CORONARY ARTERY DISEASE OVERVIEWPathogenesis, Clinical Features, Diagnostic Testing and Therapy

Hank George, FALU, CLU, FLMIHank George, FALU, CLU, FLMI

“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

What do we know about atherosclerosis?

• It is a diffuse, systemic disease of It is a diffuse, systemic disease of the arterial treethe arterial tree

• It may be present It may be present and even severeand even severe despite the absence of despite the absence of recognizedrecognized clinical symptomsclinical symptoms

• It may produce no extra mortality or It may produce no extra mortality or morbidity…until it destabilizes morbidity…until it destabilizes resulting in resulting in VULNERABLE PLAQUEVULNERABLE PLAQUE

What characterizes aVULNERABLE PLAQUE?

Typically, a non-obstructive atheroma having a central lipid core, a thin fibrous cap and a

yellowish appearance.

What can trigger an What can trigger an acute coronary acute coronary eventevent by inducing destabilization by inducing destabilization

of a vulnerable lesion?of a vulnerable lesion?

• Temperature change• Smoking a cigarette• Sexual activity• Vigorous exercise in a decondit ioned person• Acute mental stress• Pollut ion• Infection• Excess hydration• Day-to-day dietary changes• Severe periodontal disease

What is the “endothelium?”The lining covering the internal surface of blood vessels, heart

valves and bodily cavit ies

What is the role of the endothelium?

It protects the artery from injuryby maintaining an antithromboticsurface, mediating vasodilation

and inhibit ing inflammation

What is endothelial DYSFUNCTION?

Disruption of normal function, leading to vasoconstriction, endothelial inflammation

and thrombus formation

What induces DYSFUNCTION?

Inflammation, excess oxidized LDL-cholesteroland many other complex biological factors

How do we know that inflammation How do we know that inflammation occurring outside the coronary arteriesoccurring outside the coronary arteries

is associated with is 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

Coronary Artery DiseaseFour Main Presentations

SILENT ISCHEMIASILENT ISCHEMIACHRONIC STABLE ANGINA PECTORISCHRONIC STABLE ANGINA PECTORIS

ACUTE CORONARY ACUTE CORONARY SYNDROMESSYNDROMES

UNSTABLE ANGINA PECTORISUNSTABLE ANGINA PECTORISMYOCARDIAL INFARCTION MYOCARDIAL INFARCTION

SILENT ISCHEMIASILENT ISCHEMIA

• Ischemic changes on ECGs in the Ischemic changes on ECGs in the absence of clinically-recognized absence of clinically-recognized symptomssymptoms

• Most common in diabetics due to Most common in diabetics due to neuropathyneuropathy

• As significant as chronic stable As significant as chronic stable angina in terms of the subsequent angina in terms of the subsequent risk of ACS events, as well as risk of ACS events, as well as mortality and morbidity.mortality and morbidity.

CHRONIC STABLE ANGINACHRONIC STABLE ANGINA

• Episodes of chest pain and other Episodes of chest pain and other symptoms (dyspnea, fatigue) induced by symptoms (dyspnea, fatigue) induced by increased oxygen demand and relieved increased oxygen demand and relieved with cessation of inciting activity or Rxwith cessation of inciting activity or Rx

• Patients often have 2-3 times more silent Patients often have 2-3 times more silent episodes than symptomatic episodesepisodes than symptomatic episodes

• BEST CASESBEST CASES have have minimal excess minimal excess mortalitymortality when compared to the general when compared to the general populationpopulation

How does How does chronic stable anginachronic stable angina

differ from differ from unstable angina?unstable angina?

• Presents with typical Presents with typical chest pain, induced by chest pain, induced by typical symptomstypical symptoms

• May be presumptively May be presumptively diagnosed by diagnosed by symptoms onlysymptoms only

• Due to fixed Due to fixed obstructive diseaseobstructive disease

• Managed as Managed as outpatientoutpatient

• Treated medically or Treated medically or surgically – surgically – often by often by patient choicepatient choice

• Presents like MI with Presents like MI with prolonged chest prolonged chest pains, etc.pains, etc.

• Diagnosed by ECG Diagnosed by ECG and cardiac markersand cardiac markers

• Due to intraluminal Due to intraluminal thrombus formation in thrombus formation in vulnerable diseasevulnerable disease

• Managed in hospitalManaged in hospital

• Treated by Treated by percutaneous percutaneous coronary intervention coronary intervention (PCI)(PCI)

STABLESTABLE UNSTABLEUNSTABLE

CHEST PAIN EPISODECHEST PAIN EPISODEUnderwriting TriageUnderwriting Triage

• Age,Age, gendergender• CV profileCV profile• Where did patient present? ER? GP Where did patient present? ER? GP

office?office?• Were Sx typical or atypical Were 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

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; more more

sensitive and specific than CK-MBsensitive and specific than CK-MB• Degree of elevation during/after MI key to Degree of elevation during/after MI key to

long term prognosislong term prognosis• Elevates in other scenarios, including Elevates in other scenarios, including

after after noncardiacnoncardiac surgeries surgeries• These elevations are These elevations are adverse mortality adverse mortality

predictorspredictors even in even in absenceabsence of of structural/functional heart damagestructural/functional heart damage

NT-proBNPNT-proBNPFinest 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 subjects Predictive 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

Other candidates for CV screening

• HbA1-c• Cystatin C• Apolipoprotein B:A1 ratio

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?)

Disease Assessment Parameters

• Exercise ischemiaExercise ischemia• Treadmill performanceTreadmill performance• Reversible vs. irreversible lesionsReversible vs. irreversible lesions• Left ventricular ejection fraction Left ventricular ejection fraction

(LVEF)(LVEF)• Wall motion: hypokinesis, Wall motion: hypokinesis,

dyskinesis, akinesisdyskinesis, akinesis• Degree of fixed obstructive disease Degree of fixed obstructive disease

CACCACCoronary Artery CalciumCoronary Artery Calcium

• Scanned for with helical and Scanned 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 risk Very 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 for Readily available to consumers for

$200 =$200 = antiselection potential! antiselection potential!

MEDICAL MANAGEMENTMEDICAL MANAGEMENT

• Antianginals: nitroglycerin, Antianginals: nitroglycerin, isosorbide dinitrate, mononitratesisosorbide dinitrate, mononitrates

• Beta-blockers or calcium channel Beta-blockers or calcium channel blockers as alternative antianginalsblockers as alternative antianginals

• Clopidogrel, aspirin as Clopidogrel, aspirin as antithrombotic prophylaxisantithrombotic prophylaxis

• Statin prophylaxisStatin prophylaxis• Lifestyle modificationLifestyle modification

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

Does surgical management lead to Does surgical management lead to lower subsequent mortality than lower subsequent mortality than

medical management?medical management?

It depends on which study you believe!Overall, this does not matter nearly as Overall, 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 the how the patient responds to the diagnosis in terms of compliance and diagnosis in terms of compliance and

lifestyle choiceslifestyle choices

What factors should be What 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 on Current 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

……one more:one more: whether or not the whether or not the individual is individual is depresseddepressed, based on , based on

symptoms, need for treatment, symptoms, need for treatment, etc.etc.

Many recent studies have shown Many recent studies have shown that depressed CAD patients that depressed CAD patients

have significantly greater have significantly greater intermediate and longer-termintermediate and longer-term

morbidity and mortalitymorbidity and mortality

CHEST PAIN CHEST 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 of Further 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

STRESS CARDIOMYOPATHYSTRESS CARDIOMYOPATHY

• Takotsubo cardiomyopathy,Takotsubo cardiomyopathy, apical apical ballooning syndromeballooning syndrome

• 82% postmenopausal females82% postmenopausal females• Induced by severe stress, also acute Induced 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 function Normalization 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?