Coronary artery disease results from atherosclerosis causing plaque buildup in arteries. Plaques can rupture, causing clots that block blood flow and lead to heart attacks. While disease may be silent for a long time, vulnerable plaques that rupture can cause life-threatening acute coronary syndromes. Diagnosis involves testing for ischemia and imaging arteries. Treatment includes lifestyle changes, medications, and procedures like stents or bypass surgery depending on severity. Prognosis depends on extent of damage, treatment response, and risk factor control.

1. CORONARY ARTERY
DISEASE OVERVIEW
Pathogenesis, Clinical Features,
Diagnostic Testing and Therapy
Hank George, FALU, CLU, FLMIHank George, FALU, CLU, FLMI

2. “Myocardial infarction, sudden death and unstable
angina have in common a genesis of coronary
thrombosis, which develops as a result of a
ruptured vulnerable or an eroded atherosclerotic
plaque. As long as atherosclerotic lesions do not
rupture and eroded plaques do not induce
thrombosis, coronary disease may be a clinically
silent disease associated with low mortality.
Whenever plaques start to rupture and
thrombogenic material is coming into contact with
circulating blood, a situation is created
which may lead to acute coronary syndrome
associated with high mortality”
Johannes A. Schaar
Erasmus Medical College, Amsterdam
Circulation 108(2003):2636

3. What do we know
about atherosclerosis?
• It is a diffuse, systemic disease ofIt is a diffuse, systemic disease of
the arterial treethe arterial tree
• It may be presentIt may be present and even severeand even severe
despite the absence ofdespite the absence of recognizedrecognized
clinical symptomsclinical symptoms
• It may produce no extra mortality orIt may produce no extra mortality or
morbidity…until it destabilizesmorbidity…until it destabilizes
resulting inresulting in VULNERABLE PLAQUEVULNERABLE PLAQUE

4. What characterizes a
VULNERABLE PLAQUE?
Typically, a non-obstructive
atheroma having a central lipid
core, a thin fibrous cap and a
yellowish appearance.

5. What can trigger anWhat can trigger an acute coronaryacute coronary
eventevent by inducing destabilizationby inducing destabilization
of a vulnerable lesion?of a vulnerable lesion?
• Temperature change
• Smoking a cigarette
• Sexual activity
• Vigorous exercise in a deconditioned person
• Acute mental stress
• Pollution
• Infection
• Excess hydration
• Day-to-day dietary changes
• Severe periodontal disease

6. What is the “endothelium?”
The lining covering the internal
surface of blood vessels, heart
valves and bodily cavities
What is the role of the endothelium?
It protects the artery from injury
by maintaining an antithrombotic
surface, mediating vasodilation
and inhibiting inflammation

7. What is endothelial DYSFUNCTION?
Disruption of normal function, leading to
vasoconstriction, endothelial inflammation
and thrombus formation
What induces DYSFUNCTION?
Inflammation, excess oxidized LDL-cholesterol
and many other complex biological factors

8. How do we know that inflammationHow do we know that inflammation
occurring outside the coronary arteriesoccurring outside the coronary arteries
is associated withis associated with
acute coronary syndromes?acute coronary syndromes?
Because patients with systemic
inflammatory diseases such as
rheumatoid arthritis and SLE develop
endothelial dysfunction and have
excess CAD

9. Coronary Artery Disease
Four Main Presentations
SILENT ISCHEMIASILENT ISCHEMIA
CHRONIC STABLE ANGINA PECTORISCHRONIC STABLE ANGINA PECTORIS
ACUTE CORONARYACUTE CORONARY
SYNDROMESSYNDROMES
UNSTABLE ANGINA PECTORISUNSTABLE ANGINA PECTORIS
MYOCARDIAL INFARCTIONMYOCARDIAL INFARCTION

10. SILENT ISCHEMIASILENT ISCHEMIA
• Ischemic changes on ECGs in theIschemic changes on ECGs in the
absence of clinically-recognizedabsence of clinically-recognized
symptomssymptoms
• Most common in diabetics due toMost common in diabetics due to
neuropathyneuropathy
• As significant as chronic stableAs significant as chronic stable
angina in terms of the subsequentangina in terms of the subsequent
risk of ACS events, as well asrisk of ACS events, as well as
mortality and morbidity.mortality and morbidity.

11. CHRONIC STABLE ANGINACHRONIC STABLE ANGINA
• Episodes of chest pain and otherEpisodes of chest pain and other
symptoms (dyspnea, fatigue) induced bysymptoms (dyspnea, fatigue) induced by
increased oxygen demand and relievedincreased oxygen demand and relieved
with cessation of inciting activity or Rxwith cessation of inciting activity or Rx
• Patients often have 2-3 times more silentPatients often have 2-3 times more silent
episodes than symptomatic episodesepisodes than symptomatic episodes
• BEST CASESBEST CASES havehave minimal excessminimal excess
mortalitymortality when compared to the generalwhen compared to the general
populationpopulation

12. How doesHow does
chronic stable anginachronic stable angina
differ fromdiffer from
unstable angina?unstable angina?

13. • Presents with typicalPresents with typical
chest pain, induced bychest pain, induced by
typical symptomstypical symptoms
• May be presumptivelyMay be presumptively
diagnosed bydiagnosed by
symptoms onlysymptoms only
• Due to fixedDue to fixed
obstructive diseaseobstructive disease
• Managed asManaged as
outpatientoutpatient
• Treated medically orTreated medically or
surgically –surgically – often byoften by
patient choicepatient choice
• Presents like MI withPresents like MI with
prolonged chestprolonged chest
pains, etc.pains, etc.
• Diagnosed by ECGDiagnosed by ECG
and cardiac markersand cardiac markers
• Due to intraluminalDue to intraluminal
thrombus formation inthrombus formation in
vulnerable diseasevulnerable disease
• Managed in hospitalManaged in hospital
• Treated byTreated by
percutaneouspercutaneous
coronary interventioncoronary intervention
(PCI)(PCI)
STABLESTABLE UNSTABLEUNSTABLE

14. CHEST PAIN EPISODECHEST PAIN EPISODE
Underwriting TriageUnderwriting Triage
• Age,Age, gendergender
• CV profileCV profile
• Where did patient present? ER? GPWhere did patient present? ER? GP
office?office?
• Were Sx typical or atypicalWere Sx typical or atypical
• What brought it on?What brought it on?
• What brought relief?What brought relief?
• Referral to non-cardiologist?Referral to non-cardiologist?
• ManagementManagement

15. TROPONINTROPONIN
• Myocardial proteins cTnT + cTnIMyocardial proteins cTnT + cTnI
• Essential component of MI diagnosisEssential component of MI diagnosis
• Elevate from heart muscle damage;Elevate from heart muscle damage; moremore
sensitive and specific than CK-MBsensitive and specific than CK-MB
• Degree of elevation during/after MI key toDegree of elevation during/after MI key to
long term prognosislong term prognosis
• Elevates in other scenarios, includingElevates in other scenarios, including
afterafter noncardiacnoncardiac surgeriessurgeries
• These elevations areThese elevations are adverse mortalityadverse mortality
predictorspredictors even ineven in absenceabsence ofof
structural/functional heart damagestructural/functional heart damage

16. NT-proBNPNT-proBNP
Finest CV Marker EVERFinest CV Marker EVER
• Elevations due to myocardial stretchElevations due to myocardial stretch
• Elevates in all forms of cardiac diseaseElevates in all forms of cardiac disease
• Predictive of future mortality in subjectsPredictive of future mortality in subjects
free of known CV diseasefree of known CV disease
• Independent of usual CV risk factorsIndependent of usual CV risk factors
• InexpensiveInexpensive
• Recent report says protective value pay-Recent report says protective value pay-
off from this test is FANTASTICoff from this test is FANTASTIC
• Will replace subjective (treadmill, ECG)Will replace subjective (treadmill, ECG)
CV screening in underwritingCV screening in underwriting

17. Other candidates
for CV screening
• HbA1-c
• Cystatin C
• Apolipoprotein B:A1 ratio

18. Diagnostic Testing in CADDiagnostic Testing in CAD
• Resting ECGResting ECG
• Treadmill stress ECGTreadmill stress ECG
• Stress echocardiogram –Stress echocardiogram – exercise vs.exercise vs.
dobutaminedobutamine (why can’t he exercise?)(why can’t he exercise?)
• Myocardial scintigraphy (thallium,Myocardial scintigraphy (thallium,
etc.)etc.)
• Noninvasive CT angiographyNoninvasive CT angiography
• Invasive angiographyInvasive angiography (presurgical?)(presurgical?)

19. Disease Assessment Parameters
• Exercise ischemiaExercise ischemia
• Treadmill performanceTreadmill performance
• Reversible vs. irreversible lesionsReversible vs. irreversible lesions
• Left ventricular ejection fractionLeft ventricular ejection fraction
(LVEF)(LVEF)
• Wall motion: hypokinesis,Wall motion: hypokinesis,
dyskinesis, akinesisdyskinesis, akinesis
• Degree of fixed obstructive diseaseDegree of fixed obstructive disease

20. CACCAC
Coronary Artery CalciumCoronary Artery Calcium
• Scanned for with helical andScanned for with helical and
electron beam computed tomographyelectron beam computed tomography
• Extent of calcium quantifiedExtent of calcium quantified
• Range 0-400Range 0-400
• Very low riskVery low risk with scores 0-10;with scores 0-10;
just the opposite with 101-400just the opposite with 101-400
• Readily available to consumers forReadily available to consumers for
$200 =$200 = antiselection potential!antiselection potential!

21. MEDICAL MANAGEMENTMEDICAL MANAGEMENT
• Antianginals: nitroglycerin,Antianginals: nitroglycerin,
isosorbide dinitrate, mononitratesisosorbide dinitrate, mononitrates
• Beta-blockers or calcium channelBeta-blockers or calcium channel
blockers as alternative antianginalsblockers as alternative antianginals
• Clopidogrel, aspirin asClopidogrel, aspirin as
antithrombotic prophylaxisantithrombotic prophylaxis
• Statin prophylaxisStatin prophylaxis
• Lifestyle modificationLifestyle modification

22. SURGICAL MANAGEMENTSURGICAL MANAGEMENT
• Percutaneous coronary intervention,
with or without stenting (PCI)
• Coronary artery bypass grafting
(CABG)
• CABG has less long-term cardiac
morbidity in terms of symptom
recurrence
• No difference in 10 year prospective
mortality
Bravata. Annals of Internal Medicine. 147(2007):703

23. Does surgical management lead toDoes surgical management lead to
lower subsequent mortality thanlower subsequent mortality than
medical management?medical management?
It depends on which study you believe!
Overall, this does not matter nearly asOverall, this does not matter nearly as
much asmuch as (1)(1) the extent of heart damagethe extent of heart damage
andand (2)(2) how the patient responds to thehow the patient responds to the
diagnosis in terms of compliance anddiagnosis in terms of compliance and
lifestyle choiceslifestyle choices

24. What factors should beWhat factors should be
considered in potentially-considered in potentially-
insurable CAD cases?insurable CAD cases?
• Extent of myocardial damageExtent of myocardial damage
• Current myocardial function, based onCurrent myocardial function, based on
interim testinginterim testing
• Nature and extent of treatmentNature and extent of treatment
• Compliance with RxCompliance with Rx
• Risk factor improvement (BP, lipids)Risk factor improvement (BP, lipids)
• Health habit changes (quit smoking,Health habit changes (quit smoking,
exercise)…andexercise)…and

25. ……one more:one more: whether or not thewhether or not the
individual isindividual is depresseddepressed, based on, based on
symptoms, need for treatment,symptoms, need for treatment,
etc.etc.
Many recent studies have shownMany recent studies have shown
that depressed CAD patientsthat depressed CAD patients
have significantly greaterhave significantly greater
intermediate and longer-termintermediate and longer-term
morbidity and mortalitymorbidity and mortality

26. CHEST PAINCHEST PAIN
with normal coronary anatomywith normal coronary anatomy
• Mostly womenMostly women
• Chest pain has features of anginaChest pain has features of angina
• Often positive stress testOften positive stress test
• Further evaluation shows no evidence ofFurther evaluation shows no evidence of
significant obstructive coronary diseasesignificant obstructive coronary disease
• Microvascular disease often presentMicrovascular disease often present
• No significant extra mortalityNo significant extra mortality
• Substantial excess morbiditySubstantial excess morbidity

27. STRESS CARDIOMYOPATHYSTRESS CARDIOMYOPATHY
• Takotsubo cardiomyopathy,Takotsubo cardiomyopathy, apicalapical
ballooning syndromeballooning syndrome
• 82% postmenopausal females82% postmenopausal females
• Induced by severe stress, also acuteInduced by severe stress, also acute
medical illness and after surgerymedical illness and after surgery
• Presents like ACSPresents like ACS
• No obstructive lesionsNo obstructive lesions
• Normalization of left ventricular functionNormalization of left ventricular function
in 1-3 months in most casesin 1-3 months in most cases
• Supportive care onlySupportive care only
• Recurrence rate 2-10%Recurrence rate 2-10%
What is the long-term mortality risk?What is the long-term mortality risk?