dr. Ralph Kairupan, SpKJ(K)dr. Ralph Kairupan, SpKJ(K)Makassar, 23 Mei 1961Makassar, 23 Mei 1961

STATUS PERKAWINAN:STATUS PERKAWINAN:   Isteri : dr. Nova H. Kapantow, DAN, MSc.Isteri : dr. Nova H. Kapantow, DAN, MSc.

Anak-anak: Tara (16), Timothy (15), Tiffany (11)Anak-anak: Tara (16), Timothy (15), Tiffany (11)

PENDIDIKAN / SERTIFIKASI:PENDIDIKAN / SERTIFIKASI: Dokter Umum: FK UNSRAT 1987Dokter Umum: FK UNSRAT 1987

Dokter Spesialis I: FK UI 1996; Dokter Spesialis I: FK UI 1996; Dokter Spesialis II: FK UI 1999Dokter Spesialis II: FK UI 1999

Dokter Spesialis Konsultan (Kolegium PDSKJI 2004)Dokter Spesialis Konsultan (Kolegium PDSKJI 2004)

PEKERJAAN:PEKERJAAN: Staf Bagian Psikiatri FK Unsrat 1987 – Staf Bagian Psikiatri FK Unsrat 1987 –

Sekretaris Pusat Bimb. & Kons. LP3 UNSRAT 2004 –Sekretaris Pusat Bimb. & Kons. LP3 UNSRAT 2004 –Anggota Tim SP4 UNSRAT 2006 - Anggota Tim SP4 UNSRAT 2006 -

COMORBIDITY OF COMORBIDITY OF ANXIETY – DEPRESSION IN ANXIETY – DEPRESSION IN

CAD PATIENTS : CAD PATIENTS :

HOW TO MANAGEHOW TO MANAGE

Ralph KairupanRalph Kairupan

What is Comorbidity?

The term comorbidity first appeared in the psychological & psychiatric literature in the mid 1980’s (1986: 2 articles).

Since that time there has been a dramatic increase in interest in this topic as reflected in the number of journal articles containing the term comorbidity in the title. 1993: 243 artikel. Now: >>>

What is Comorbidity?

Definition (Blashfield): The co-occurence of different diseases in the same individual.Possible comorbidities: Psycho-somatic:

Anxiety & CAD ; Depression & CAD Somato-psychic:

CAD & Anxiety ; CAD & Depression No causal relationship vv:

Anxiety & CAD ; Depression & CAD Anxiety – Depression - CAD

ANXIETY (PD) & CAD

Anxiety (PD) & CADAnxiety (PD) & CAD

Anxiety will increase the mortality & morbidity of Anxiety will increase the mortality & morbidity of CAD. PD is one of the anxiety disorders that must CAD. PD is one of the anxiety disorders that must be recognized.be recognized.

Anxiety Anxiety CAD: Etiology; Precipitating; CAD: Etiology; Precipitating; Exacerbating; Worsening prognosis; Cause of Exacerbating; Worsening prognosis; Cause of sudden death.sudden death.

Among individuals with CAD, anxiety has been Among individuals with CAD, anxiety has been found to be associated with an approx. found to be associated with an approx. 6 fold6 fold increase in the risk of sudden cardiac death.increase in the risk of sudden cardiac death.

21% of CAD patients admitting ICCU suffer from PD Carter C, et al. Psychosomatic, 1992;33:302-09

6% of coronary angiography suffer from anxiety Katon W, et al. Am J Med, 1988;18:315-23

59% of chest pain complaining from treated CAD patients is caused by anxiety Ros E, et al. Dig Dis sei, 1977;42:1344-53

CardiovascularConsequences

of Anxiety

Arrhythmias

Hypertension

Chest pain

Coronary artery disease

Cardiovascular Symptoms of Anxiety

Increased cardiac awarenessPalpitations (often unassociated with arrhythmia)Chest painDyspepsiaFatigueDizzinessSweatingTremor

Heart Disease, Cardiovascular Symptoms and Anxiety Are All

InterrelatedHEART

DISEASE

CARDIOVASCULAR SYMPTOMS

ANXIETY

Jefferson JW, 1996

ANXIETY AMYGDALA

CORTEX AREA

COGNITIVE DISTORTIO

N

PERIAQUADUCT (GREY)

next….ANXIETY BEHAVIOR

PARABRACHIAL NUCLEUS

HYPERVENTILATION

HYPOTHALAMUS

(LATERAL)

SYMPHATIC HYPERACTIVITY

HYPOTHALAMUS PVN

ENDOCRINE

ACTIVATION

VAGUS (DORSAL MOTOR) NUCLEUS

GIT DISTURBANC

ES

PONTIN (CAUDAL) NUCLEUS

EASILY STARTLE

DSTRIATUM

MOTORIC HYPERACTIVI

TY

Mental Stress

Central and Autonomic Nervous System Activity

CatecholamineHeart Rate

Blood Pressure

Plasma volumeCoronary circulation

Platelet activity

Electrical instabilityDemand O2Supply O2

VTach, VFibPlaque ruptureCoronary thrombosis

AtherosclerosisPrior MILV dysfunction

Suddendeath

Acute CoronarySyndrome

DEPRESSION & CAD

Depression & CADDepression & CAD

Since mid 1970s, epidemiologists Since mid 1970s, epidemiologists began to report consistent associations began to report consistent associations between depression and cardiovascular between depression and cardiovascular morbidity & mortalitymorbidity & mortality

Many large studies have identified Many large studies have identified depression as depression as a significant independent a significant independent risk factorrisk factor for both first MI & CV for both first MI & CV†, with †, with an adjusted relative risk 1,5 - 2an adjusted relative risk 1,5 - 2

Am J Psychiatry 1998;155:4-11Epidemiology,1993;4:285-294Arch Intern Med.1998;158:1422-1426

Cont’d…Cont’d…

Among individuals with established Among individuals with established ischemic heart disease, depression has ischemic heart disease, depression has been found to be associated with an been found to be associated with an approx. 3-4 fold increase in the risk of approx. 3-4 fold increase in the risk of subsequent cardiovascular morbidity & subsequent cardiovascular morbidity & mortalitymortality

The prevalence of major depression in The prevalence of major depression in CAD pts is 15 – 23%CAD pts is 15 – 23%

Circulation 2000;102:1773-1779JAMA 1993;270:1819-1825Am J Cardiol 2001;88:337-341

Symptoms of Depression

Emotional disturbances

Cognitive disturbances

Psychomotor disturbances

Vegetative disturbances

Somatic disturbances

Depression & CAD Risk Factors

Less –(un)compliance:Depression marker

Smoking:smoking cessation

Hypertension:Autonomic system

DMGlycemia control

Biologically Plausible Mechanism Linking Biologically Plausible Mechanism Linking Depression with CADDepression with CAD

Less Less compliance?compliance?

AbnormalAbnormalVasomotion?Vasomotion?

AbnormalAbnormalInflammatoryInflammatory

ResponsesResponses

SickerSicker

AutonomicAutonomicDysfunction?Dysfunction?

Hyper-adrenergic?Hyper-adrenergic?

Abnormalities inAbnormalities inPlatelet function?Platelet function?

Depression orDepression orstressstress →←

↑

↓

Abnormal Platelet Abnormal Platelet FunctionFunction

Increased platelet activityIncreased platelet activity

Increased levels of platelet factor 4 Increased levels of platelet factor 4 (PF4) & (PF4) & - thromboglobulin - thromboglobulin

Increased platelet reactivity to serotoninIncreased platelet reactivity to serotonin

Decreased platelet reactivity to ADPDecreased platelet reactivity to ADP

Eur HJ 2004;25:3-9

Less ComplianceLess Compliance

Less compliance / non adherence to Less compliance / non adherence to risk factor modification in many medical risk factor modification in many medical conditions :conditions :

- smoking cessation- smoking cessation

- poor glycemic control in DM pts- poor glycemic control in DM pts

- poor adherence to prescribed - poor adherence to prescribed

medicinemedicine

Eur HJ 2004;25:3-9Eur HJ 2004;25:3-9

Autonomic DysfunctionAutonomic Dysfunction

Autonomic dysfunction is reflected by Autonomic dysfunction is reflected by decreased Heart Rate Variability (HRV)decreased Heart Rate Variability (HRV)

Pts with anxiety & depression have reduced Pts with anxiety & depression have reduced HRVHRV

Low HRV is a powerful predictor of sudden Low HRV is a powerful predictor of sudden cardiac deathcardiac death

A direct association between the severity of A direct association between the severity of depressive symptoms & modulation of depressive symptoms & modulation of cardiovagal activity was foundcardiovagal activity was found

Eur HJ 2004;25:3-9Eur HJ 2004;25:3-9

Abnormal VasomotionAbnormal Vasomotion

Depression is independent predictor of Depression is independent predictor of reactive hyperemia in brachial artery reactive hyperemia in brachial artery flow-mediated dilatation (FMD) in the flow-mediated dilatation (FMD) in the absence of other conventional risk absence of other conventional risk factors factors

Depression is associated with Depression is associated with endothelial dysfunctionendothelial dysfunction

Eur Heart J 2004;25:3-9Eur Heart J 2004;25:3-9

Abnormal inflammatory Abnormal inflammatory responsesresponses

Soluble Intercellular adhesion molecule Soluble Intercellular adhesion molecule 1 (sICAM-1) and C-reactive protein 1 (sICAM-1) and C-reactive protein (CRP) following Cardiac Events are (CRP) following Cardiac Events are higher in depressed pts than in non-higher in depressed pts than in non-depressed ptsdepressed ptsCRP and sICAM are serum CRP and sICAM are serum inflammatory markersinflammatory markers

Am J Psychiatry 2004;161:271-277Am J Psychiatry 2004;161:271-277

AgentAgent Cardiovascular effectsCardiovascular effects

SSRISSRIBenign bradycardiaBenign bradycardia

TricyclicTricyclic

Tachycardia, arrhythmias, Postural Tachycardia, arrhythmias, Postural

hypotension, QT interval hypotension, QT interval

PsychostimulantsPsychostimulantsMild tachycardia and Mild tachycardia and

hypertensionhypertension

TrazadoneTrazadone Postural hypotensionPostural hypotension

BenzodiazepinesBenzodiazepines --------------

Barsky AJ in Braunwald E, Zipes DP, Libby P: Heart Disease 2001Barsky AJ in Braunwald E, Zipes DP, Libby P: Heart Disease 2001

CARDIOVASCULAR EFFECT OF CARDIOVASCULAR EFFECT OF ANXIOLYTIC & ANTIDEPRESSANTSANXIOLYTIC & ANTIDEPRESSANTS

SummarySummary

CAD & Anxiety - Depression CAD & Anxiety - Depression highly highly prevalent prevalent decrease QOL decrease QOL

Depression Depression per seper se is an independent is an independent risk factor of cardiac eventrisk factor of cardiac event

Several behavioral & pathophysiologic Several behavioral & pathophysiologic factors link anxiety - depression & CADfactors link anxiety - depression & CAD

SummarySummary

• Anxiety & Depression influence Anxiety & Depression influence Cardiovascular morbidity & mortalityCardiovascular morbidity & mortalityManagement of CAD + Anxiety & Management of CAD + Anxiety & Depression should includes CBT & Depression should includes CBT & Medical TherapyMedical TherapyShort-term therapy with Short-term therapy with Benzodiazepines and long-term therapy Benzodiazepines and long-term therapy with SSRI are beneficialwith SSRI are beneficial

GOD BLESS YOU

Thank You