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Coronary Artery Disease (CAD)Coronary Artery Disease (CAD)

Arterial HypertensionArterial Hypertension

Blagoi Marinov, MD, PhDBlagoi Marinov, MD, PhD

Pathophysiology Dept.Pathophysiology Dept.

Medical University of PlovdivMedical University of Plovdiv

Coronary arteriesCoronary arteries

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OO22 regimen of the heartregimen of the heart

TDP of left ventricle

Coronaryresistance

Heartrate

Contractile state

Wall stress

О2 extraction

О2 content

Coronaryblood flow

О2 requirements О2 delivery

rate

Risk Risk ffactors for Atherosclerosisactors for Atherosclerosis

Major Lesser, Uncertain, or Nonquantitated

Nonmodifiable

Increasing age Obesity

Male gender Physical inactivity

Family history Stress ("type A" personality)

Genetic abnormalities Postmenopausal estrogen deficiency

High carbohydrate intake

Potentially ControllablePotentially Controllable

Hyperlipidemia Alcohol

Hypertension Lipoprotein Lp(a)

Cigarette smoking Hardened (trans)unsaturated fat intake

Diabetes Chlamydia pneumoniae

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Atherosclerosis – the most important etiologic factor

PPathogenetic events, and clinical complications of athogenetic events, and clinical complications of atherosclerosis in the coronary arteriesatherosclerosis in the coronary arteries

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DefinitionDefinition

IschemiaIschemia refersrefers toto anan insufficientinsufficient amountamountofof bloodblood SinceSince thethe coronarycoronary arteriesarteries areareofof bloodblood.. SinceSince thethe coronarycoronary arteriesarteries arearethethe onlyonly sourcesource ofof bloodblood forfor thethe heartheart musclemuscleitsits bloodblood supplysupply willwill suffersuffer tremendouslytremendously..

Myocardial IschemiaMyocardial Ischemia

Myocardium becomes ischemic within 10 Myocardium becomes ischemic within 10 d f l id f l iseconds of coronary occlusionseconds of coronary occlusion

Working Working cells remain viable for up to 20 cells remain viable for up to 20 minutesminutes–– Anaerobic mechanisms kick inAnaerobic mechanisms kick in

Lactic acidLactic acidLactic acidLactic acid

Free radical damage, especially after reperfusionFree radical damage, especially after reperfusion

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Ischemic episodeIschemic episode

SeveritySeverity

DurationDuration

FrequencyFrequency

Pain

Ischemia

CAD classificationCAD classificationStable anginaStable anginaU t bl iU t bl iUnstable anginaUnstable anginaAtypical anginaAtypical angina (Prinzmetal)(Prinzmetal)Myocardial infarctionMyocardial infarctionAtherosclerotic Atherosclerotic myocardiosclerosismyocardiosclerosismyocardiosclerosismyocardiosclerosisSilent ischemiaSilent ischemiaSudden cardiac deathSudden cardiac death

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Stable anginaStable angina

Chest pain with exertionChest pain with exertionpp

May radiate, may have diaphoresis, SOB, pallorMay radiate, may have diaphoresis, SOB, pallor

Relief with rest or nitratesRelief with rest or nitrates

Increased О2

demand

Decreased О2

delivery

Morphological substrateMorphological substrate

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Treatment for Stable AnginaTreatment for Stable Angina

DrugDrugNit tNit t–– NitratesNitrates

–– Beta blockersBeta blockers

–– Calcium Channel BlockersCalcium Channel Blockers

–– StatinsStatins

Invasive cardiologyInvasive cardiologyInvasive cardiology Invasive cardiology –– PTCA PTCA

–– StentStent

SurgerySurgery–– BypassBypass

Acute Coronary SyndromeAcute Coronary Syndrome

Atherosclerotic Plaque

Stable Plaque Unstable Plaque

Stable Angina Acute Coronary Syndrome

SustainedI h i

TransientI h i / Ischemia

MyocardialInfarction

Ischemia/UnstableAngina

Necrosis

FrequencyFrequencySeveritySeverityMagnitudeMagnitudeDurationDuration

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atherosclerotic plaqueatherosclerotic plaque

blood clot sticking to plaque

narrowed lumen

Advances in interventional cardiologyAdvances in interventional cardiology

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PTCAPTCA: Percutaneous Transluminal : Percutaneous Transluminal Coronary AngioplastyCoronary Angioplasty

Invasive, but nonsurgical technique to Invasive, but nonsurgical technique to reduce frequency and severity of chest reduce frequency and severity of chest discomfortdiscomfort May also be used during evolving MIMay also be used during evolving MI

Procedure performed under fluoroscopic Procedure performed under fluoroscopic guidance in cardiac cath labguidance in cardiac cath labguidance in cardiac cath labguidance in cardiac cath lab Balloon inflation may be repeated until lesion is Balloon inflation may be repeated until lesion is

reduced or eliminatedreduced or eliminated

Stents may be placed at time of procedureStents may be placed at time of procedure

CABGCABG: Coronary Artery Bypass Graft: Coronary Artery Bypass Graft

Most common cardiac surgeryMost common cardiac surgeryIndicated for patients who do not respond to Indicated for patients who do not respond to medical management of CAD or when disease medical management of CAD or when disease progression is evidentprogression is evidentTo be bypassed vessels should have proximal To be bypassed vessels should have proximal lesions with > 70% occlusionlesions with > 70% occlusionMost effective when good ventricular functionMost effective when good ventricular functionMost effective when good ventricular function Most effective when good ventricular function remains and ejection fraction is more than 40remains and ejection fraction is more than 40--50%50%Requires Cardiopulmonary bypass during Requires Cardiopulmonary bypass during surgerysurgery

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Myocardial infarctionMyocardial infarction ((MIMI))

Ischemic necrosis of the part of myocardium

Transmural Transmural

NonNon--transmuraltransmural ((subendocardial,subendocardial, withoutwithout QQ wavewave))

p y(more frequently on the left).

G l h t i tiGeneral characteristics

Myocardium becomes hypoxic

Shift to Anaerobic Respiration

Waste products release/hypoxic injury

Cardiac output impaired

Pathogenesis of MIPathogenesis of MI

Time !

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Myocardial ChangesMyocardial Changes

Myocardial Myocardial stunningstunning–– Temporary loss of contractility that persists for Temporary loss of contractility that persists for

hours to dayshours to days

Myocardial Myocardial hibernationhibernation–– Chronically ischemic; Chronically ischemic; myocytesmyocytes are are

hibernating to preserve function until hibernating to preserve function until g pg pperfusion can be restoredperfusion can be restored

Myocardial Myocardial remodellingremodelling–– Loss of contractility mediated by Loss of contractility mediated by AngAng II, II,

catecholaminescatecholamines, and inflammatory cytokines, and inflammatory cytokines

Signs and symptoms of MISigns and symptoms of MI

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ECG changesECG changes

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Change in serum enzymesChange in serum enzymes

ImmediateImmediate Post MI Post MI TxTx

Reduce myocardial workloadReduce myocardial workload

Prevent Prevent RemodelingRemodeling

Reduce chances of Reduce chances of reocclusionreocclusion

Reduce oxidative stress (reperfusion injury)Reduce oxidative stress (reperfusion injury)

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LongLong--termterm Post MI TreatmentPost MI Treatment

LifestyleLifestyleDietDiet–– DietDiet

–– Exercise Exercise –– Cardiac RehabCardiac Rehab

–– Stress managementStress management

DrugsDrugs–– Antiplatelet: aspirin, clopidogrelAntiplatelet: aspirin, clopidogrelp p , p gp p , p g

–– Beta blockerBeta blocker

–– Statin medicationStatin medication

–– Treat risk factors (HTN, lipid, smoke, etc.)Treat risk factors (HTN, lipid, smoke, etc.)

Complications of MIComplications of MI

Disorders of rhythm and conductionDisorders of rhythm and conduction SupraventricularSupraventricular

VentricularVentricular ((tachicardiatachicardia, , fibrillationsfibrillations))

Rupture of post infarction aneurismRupture of post infarction aneurism

PericarditisPericarditis ((Dressler syndromeDressler syndrome))

Post infarction anginaPost infarction angina (20(20--30 %)30 %)

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PrognosisPrognosis of MIof MI

Acute MI is associated with a Acute MI is associated with a 30% mortality rate30% mortality rate; half of ; half of the deaths occur prior to arrival at the hospital.the deaths occur prior to arrival at the hospital.p pp p

An additional An additional 55--10%10% of survivors of survivors die within the first yeardie within the first yearafter their MI.after their MI.

Approximately Approximately half of all patientshalf of all patients with an MI are with an MI are rehospitalized within 1 yearrehospitalized within 1 year of their index event.of their index event.

Overall, Overall, prognosis is highly variableprognosis is highly variable and depends largely and depends largely on the extent of the infarct, the residual LV function, and on the extent of the infarct, the residual LV function, and whether the patient underwent revascularization.whether the patient underwent revascularization.

Screening of different forms Screening of different forms of CADof CAD

Stress testStress test CoronaryCoronaryangiographyangiography

ElectroElectro--cardiogramcardiogram

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ARTERIAL HYPERTENSIONARTERIAL HYPERTENSION

Blood pressure levels*Blood pressure levels*

SystolicSystolic DiastolicDiastolic LevelLevel

120120 8080 OptimalOptimal

< 130< 130 < 85< 85 NormalNormal

130130--139139 8585-- 8989 Normal borderlineNormal borderline

140 140 --159159 90 90 -- 9999 Mild hypertensionMild hypertension

160160 179179 100100 109109 Moderate hypertensionModerate hypertension160160--179179 100100--109109 Moderate hypertensionModerate hypertension

> 179> 179 > 109> 109 Severe hypertensionSevere hypertension

> 140> 140 < 90< 90Maximum or systolic Maximum or systolic

hypertensionhypertension

*Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and treatment of High Blood Pressure

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CCardiac output and peripheral resistance ardiac output and peripheral resistance in blood pressure regulationin blood pressure regulation

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The burden of hypertensionThe burden of hypertension(distribution by age and sex*)(distribution by age and sex*)

*CDC. National Health Survey, 2005

Types of HypertensionTypes of Hypertension

Essential Hypertension (Primary)

Secondary Hypertension

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Risk factors for arterial Risk factors for arterial hypertensionhypertension

Primary

NaCl rich diet Stress

Secondary

Hypercholesterolemia Hypercholesterolemia Prediabetic state Overweight Sedentary lifestyle Alcohol abuse

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Medium caliber arteries are Medium caliber arteries are the most affectedthe most affected

Genetic backgroundGenetic background

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Pathogenetic units Pathogenetic units for arterial hypertensionfor arterial hypertension

Neurogenic RenalEndocrine

Hypothalamo-pituitary axis

g

Pressor dominancein CNS

Sympathetic nervous system

Renal

RAAS Renal

depressor system

Cardiovascular

Total peripheral resistance (TPR)Hypervolemia

Cardiac output (CO)

Pathogenesis of Hypertension

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Symptoms and signsSymptoms and signs

Almost always asymptomaticAlmost always asymptomatic

Dyspnea most commonDyspnea most common

Headache,Dizziness,Tinnitus,FaintingHeadache,Dizziness,Tinnitus,Fainting not not correlated with hypertensioncorrelated with hypertension

Symptoms poorly correlated to degree of Symptoms poorly correlated to degree of hypertensionhypertensionhypertensionhypertension

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Consequence of HTNConsequence of HTN

(CHF)

Staging of arterial hypertensionStaging of arterial hypertension

Labile hypertensionLabile hypertensionLabile hypertensionLabile hypertensionIncreased COIncreased CO

Normal TPRNormal TPR

Stable hypertensionStable hypertensionIncreased TPRIncreased TPR

Normal CONormal CONormal CONormal CO

Organ damage and complicationsOrgan damage and complicationsCompensatedCompensated

DecompensatedDecompensated

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Complications of HypertensionComplications of Hypertension

It can always get worse …It can always get worse …

RenalA t l l h iti

CardiovascularCoarctation of aorta

Secondary Hypertension

Acute glomerulonephritisChronic renal diseasePolycystic diseaseRenal artery stenosisRenal artery fibromuscular dysplasiaRenal vasculitisRenin-producing tumorsEndocrineAdrenocortical hyperfunction

Coarctation of aortaPolyarteritis nodosa (or other vasculitis)Increased intravascular volumeIncreased cardiac outputRigidity of the aortaNeurologic (Psychogenic)Increased intracranial pressureSleep apneaAdrenocortical hyperfunction

Exogenous hormones Sympathomimetics, PheochromocytomaAcromegalyHypothyroidism (myxedema)Hyperthyroidism (thyrotoxicosis)Pregnancy-induced

p pAcute stress, including surgery

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Antihypertensive AgentsAntihypertensive Agents

General Classes of Agents:General Classes of Agents:General Classes of Agents:General Classes of Agents: DiureticsDiuretics

Sympatholytic agents Sympatholytic agents blockers (central)blockers (central)

blockers (peripheral)blockers (peripheral)

VasodilatorsVasodilators

Agents which interfere with the RAASAgents which interfere with the RAAS ACE inhibitorsACE inhibitors

Angiotensin receptor blockersAngiotensin receptor blockers

Thank you !