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Transcript of Coronary Heart Disease & Depression : The Bi-Directional Relationship Madeleine Lloyd MS, RN, FNP,...
Coronary Heart Disease & Depression:
The Bi-Directional Relationship
Coronary Heart Disease & Depression:
The Bi-Directional Relationship
Madeleine Lloyd MS, RN, FNP, MHNPMadeleine Lloyd MS, RN, FNP, MHNP
Ana Mola MA, RN, ANPAna Mola MA, RN, ANP
Global Burden of DiseaseGlobal Burden of Disease
CAD & MDD will be the 1 &2 contributors to the burden of disease by the year 2020.
•Murray, CL “Alterantive projections of mortality and disability by cause 1990-2020:Global Burden Disease Study” Lancet May 1997 vol. 349, pp 1498-1504
CDC Data 1979-2002
400
420
440
460
480
500
520
'80 '82 '84 '86 '88 '90 '92 '94 '96 '98 '00 '02
Dea
ths
in T
ho
usa
nd
s
WomenMen
CVD Mortality in US Women Is Not Declining
CVD Mortality in US Women Is Not Declining
AHA. Heart Disease and Stroke Statistics–2005 Update. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.
NCEP ATP II NCEP ATP IIINCEP ATP I
434,000
494,000
Global Burden of DiseaseGlobal Burden of Disease
WHO 2002 MEN WOMEN
Hypothalamic-Pituitary-Adrenal (HPA) axis in depression
Hypothalamic-Pituitary-Adrenal (HPA) axis in depression
Endothelium-Teflon ResistantEndothelium-Teflon Resistant
Tunica adventitia
Tunica media
Tunica intima
Endothelium
Subendothelial connective tissue
Internal elastic membrane
Smooth muscle cells
Elastic/collagen fibers
External elastic membrane
Ross, R. Nature, 1993; 362: 801-809. 1993;362:801-809.
LDL-small dense particlesLDL-small dense particles
LDLLDL
Mackness MI et al. Biochem J 1993;294:829-834.
EndotheliumEndothelium
Vessel Lumen-Teflon ResistentVessel Lumen-Teflon ResistentMonocyteMonocyte
oxidized LDLoxidized LDL
Macrophages Macrophages engulf LDLengulf LDL
Adhesion Modules-Adhesion Modules-increase monocytes increase monocytes
adherenceadherence
CytokinesCytokines
Atherosclerosis is an Inflammatory DiseaseLDL pro-inflammatory & HDL anti-inflammatory
Foam Cell-increase Foam Cell-increase ANGIOTENSIN II, ANGIOTENSIN II,
PAI, -pro-PAI, -pro-thrombotic state & thrombotic state &
decrease NOdecrease NOHDL Promote Cholesterol EffluxHDL Promote Cholesterol Efflux
HDL InhibitHDL InhibitOxidationOxidation
of LDLof LDL
Libby, P. et al. Circulation 2005;111:3481-3488
Plaque Morphology and Ischemic Impact
Pathophysiology in MotionPathophysiology in Motion
Bi-Directional Biological Mechanisms
Bi-Directional Biological Mechanisms
Pro-arrhythmic mechanisms-low HRV is a strong predictor of SCD after MI strongly exists in depressed patients then non-depressed patients with CAD
Plasma catecholamines provoke arrhythmias, myocardial ischemia and SCD are elevated in depressed patients
Depression is associated with serotonin platelet activation and cytokines that may increase the risk of developing CAD or, in patients with established CAD, of myocardial infarction.
Grippo, A. Neuroscience and Beh Reviews 2002 26: 941-962Grippo, A. Neuroscience and Beh Reviews 2002 26: 941-962
Depression and the HeartDepression and the Heart
Recognized in language Recognized in language and literatureand literatureBut scientific evidence But scientific evidence lacking!lacking!First credible studies by First credible studies by Meyer Friedman & Ray Meyer Friedman & Ray Rosenman following Rosenman following WWIIWWIIHowever, by mid-1970’s However, by mid-1970’s type A’s effect vanishedtype A’s effect vanished
Stirling County StudyCardiovascular Deaths Stirling County Study
Cardiovascular Deaths
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
Major Depression No major depression
P = 0.03
Mo
rtal
ity
Rat
e
Murphy 1987
1000 Community residents followed 16 yrs
0
5
10
15
20
25
30
0 1 2 3 4 5 6Months After Heart Attack
Mor
talit
y (%
)
183
Frasure-Smith N et al. JAMA. 1993;270:1819-1825.
Depressed (n = 35)Nondepressed (n = 187)
Depression Associated With Increased Mortality Post-Myocardial Infarction
80
85
90
95
100
0 100 200 300 400
Time After Discharge for MI (Days)
Su
rviv
al F
ree
of C
ard
iac
Mo
rta
lity,
Cu
mu
lativ
e (
%)
Not Depressed (BDI < 10)
Depressed (BDI ≥ 10)
Frasure-Smith N et al. Psychosom Med. 1999;61:18-20.
Depression and 1-Year Post-Myocardial Infarction (MI) Cardiac Mortality
Depression and 1-Year Post-Myocardial Infarction (MI) Cardiac Mortality
N = 896
Odds Ratio = 3.4 (1.8-6.7)
P < .001
60
70
80
90
100
100 365 730 1095 1460 1825
Time After Discharge for MI (Days)
Su
rviv
al F
ree
of C
ard
iac
Mo
rta
lity,
Cu
mu
lativ
e (
%)
BDI < 5
BDI 5-9
BDI 10-18
BDI ≥ 19
Lespérance,2000.
N = 896
Long-Term Survival Impact of Increasing Levels of Post-MI Depression
Long-Term Survival Impact of Increasing Levels of Post-MI Depression
N = 896
Lower Social Support Depression
14600 365 730 1095
100%
90%
80%14600 365 730 1095
100%
90%
80%
Time After Discharge for MI (Days) Time After Discharge for MI (Days)
Sur
viva
l Fre
e of
Car
dia
c M
orta
lity,
Cu
mul
ativ
e (%
)
Anxiety Anger
14600 365 730 1095
100%
90%
80%14600 365 730 1095
100%
90%
80%
Sur
viva
l Fre
e of
Car
dia
c M
orta
lity,
Cu
mul
ativ
e (%
)
Time After Discharge for MI (Days) Time After Discharge for MI (Days)
The Prognostic Impact of Depression The Prognostic Impact of Depression
N = 896
N = 896 N = 896
BDI < 10Depressed BDI>10
SADHART: Objectives
PrimaryPrimary To evaluate the safety and To evaluate the safety and
efficacy of Sertraline as a efficacy of Sertraline as a treatment of depression in treatment of depression in patients with AMI or patients with AMI or unstable anginaunstable angina
SecondarySecondary Antidepressant response in Antidepressant response in
“more severe” subset of “more severe” subset of patients (baseline HAM-D patients (baseline HAM-D > 18, 2 prior episodes of > 18, 2 prior episodes of major depression) major depression)
Improvement in quality of Improvement in quality of life and functional status life and functional status with Sertralinewith Sertraline
Efficacy in Post-MI Depression:Week-24 Responder Rates for
Sertraline vs Placebo
78%72%
59%
45%51
55%
0
20
40
60
80
100
No Prior Episode Any RecurrentDepression
2 Prior Episodes andHAM-D ≥ 18
Res
pon
der
Rat
es (
%)
SertralinePlacebo
90 93 96
P ≤ .058
90
P ≤ .003
50
P ≤ .001
40
.
ENRICHD TRIAL ENRICHD TRIAL 2481 MI patients (33,780 screened)2481 MI patients (33,780 screened) 1084 Women 1397 Men 8 centers1084 Women 1397 Men 8 centers
Objective Effect of CBT vs. treatment as usual on all-cause mortality and
nonfatal reinfarction in pt with an AMI and/or low perceived social support
Results Antidepressant drug use was associated with a lower risk of
death and non-fatal MI (H.R. 0.67) Improvement in psychosocial risk factors with intervention but
no improvement in medical outcome (death, reinfarction) Difference between the two groups were modest and small
Berkman, L.F., et al. JAMA 2003 289 (23):3171-3Berkman, L.F., et al. JAMA 2003 289 (23):3171-3
ENRICHD-sub studies:Impact of PE on MDD and LSS
ENRICHD-sub studies:Impact of PE on MDD and LSS
982 pt (47%) reported they exercise regularly 6 months 982 pt (47%) reported they exercise regularly 6 months after AMIafter AMI
Pt who did not exercise tended to be less well educated Pt who did not exercise tended to be less well educated and lower household income and more severe CADand lower household income and more severe CAD
Exercise was associated with lower levels of depression, Exercise was associated with lower levels of depression, reduced depressive symptoms and increased survivalreduced depressive symptoms and increased survival
Despite failure of CBT to reduced mortality risk in this Despite failure of CBT to reduced mortality risk in this population, exercise maybe a valuable additionpopulation, exercise maybe a valuable addition
Blumenthal: 2004 Am. College of Sports medicine36:746-755
Myocardial Infarction and Depression-Intervention Trial (MIND-IT)
Myocardial Infarction and Depression-Intervention Trial (MIND-IT)
Mirtazapine/Placebo for BDI > 10 (n=190) or care as usual (n=130)
Citalopram as an alternative if nonresponsive after 8wks or refusal
CAU pt not aware of research Dx 27months with primary end point of new events and
secondary end point of cardiac function 1 yr after MI, the course of post MI MDD and quality of life
No treatment for first 3 months after AMI to allow for natural recovery of a transient reactive MDD
MIND IT: Sub-studiesMIND IT: Sub-studies
Explored the relationship between LV function and depression in the first year post MI
1989 pts monitored LVEF Strong associated between lower
LVEF and higher depression rates MI pts younger than 60yr had a 2
fold increased risk for developing MDD
2 strong predictors of post MI depression are young age and low LEVF
CREATE (Canadian Cardiac Randomized Evaluation of Antidepressant and
Psychotherapy Efficacy)
CREATE (Canadian Cardiac Randomized Evaluation of Antidepressant and
Psychotherapy Efficacy) IPT and Citalopram alone or in
combination in the treatment of MDD in 280 stable CAD pts.
12 weeks of Tx is more effective in reducing MDD symptoms in CAD pts.
Tolerability and safety of each treatment in comparison to control.
RESULTS THIS SUMMER
Frassure-Smith, Psychosomatic Medicine 68:87-93 (2006)
Evidence for Depression as an Independent Risk factor for CAD
Evidence for Depression as an Independent Risk factor for CAD
GOODGOOD
1.1. Strength of AssociationStrength of Association
2.2. PredictionPrediction
3.3. ConsistencyConsistency
4.4. Dose-response Effect Dose-response Effect
FAIRFAIR
5.5. SpecificitySpecificity
6.6. Biological PlausibilityBiological Plausibility
INSUFFICIENT EVIDENCEINSUFFICIENT EVIDENCE
7.7. Cardiac risk reduction in Cardiac risk reduction in response to treatmentresponse to treatment for for depression.depression.
Wulsin, L.R; Harv Rev Psychiatry. March/April 2004Wulsin, L.R; Harv Rev Psychiatry. March/April 2004
Criteria for Major DepressionCriteria for Major Depression
Depressed moodDepressed mood Diminished interest or pleasureDiminished interest or pleasure
5 or more of the following Sx present for > 2 weeks:5 or more of the following Sx present for > 2 weeks: Fatigue or loss of energyFatigue or loss of energy Diminished ability to concentrateDiminished ability to concentrate Insomnia or hypersomniaInsomnia or hypersomnia Weight loss or weight gainWeight loss or weight gain Feelings of worthlessness or excessive guiltFeelings of worthlessness or excessive guilt Psychomotor agitation or retardationPsychomotor agitation or retardation Recurrent thoughts of death or suicidal ideation Recurrent thoughts of death or suicidal ideation
or attemptor attempt
One or the other required
When to suspect depression in cardiac ptsWhen to suspect depression in cardiac pts
Symptoms:Symptoms: chronic tiredness, wt loss, chronic tiredness, wt loss, insomnia, recent onset of irritability or angerinsomnia, recent onset of irritability or anger
Impairment:Impairment: reduced social contact, poor reduced social contact, poor ADLs, reduced interest, difficulty coping with ADLs, reduced interest, difficulty coping with recent losses and stressesrecent losses and stresses
Medical Management Problems: Medical Management Problems: chronic chronic anxiety, poor medication compliance or risk anxiety, poor medication compliance or risk factor modificationfactor modification
Tools for Assessment of Depression in Clinical Practice
Tools for Assessment of Depression in Clinical Practice
Patient Health Questionnaire (PHQ-9) and (PHQ-2)
Beck Depression Inventory (Self-report)
Zung Self-rating Depression Scale (self report)
Center for Epidemiologic Studies-Depression (self report)
Hamilton Depression Scale (Administered)
Meta-Analysis of the Adverse Effect of Depression on Patient
Adherence
Meta-Analysis of the Adverse Effect of Depression on Patient
Adherence
Compared to Compared to nondepressed patients, nondepressed patients, the odds are 3 times the odds are 3 times greater that depressed greater that depressed patients would be patients would be nonadherent with medical nonadherent with medical treatment treatment recommendationsrecommendations
DiMatteo MR, et al. Arch Intern Med. 2000;160(14):2101-2107.
Depression Is AssociatedWith ↑% Smoking
Depression Is AssociatedWith ↑% Smoking
0
5
10
15
20
None Minor Major
Depression Group
% S
mok
ing
p<0.001; Major>Nonep<0.01; Minor>None N=4225
Adjusted for demographics, medical comorbidity, diabetes severity,diabetes type and duration, treatment type,HbA1c and clinic. Katon et al, Diabetes Care, 2004
Bi-Directional ConclusionsBi-Directional Conclusions
PSYCHIATRYPSYCHIATRY
Depression is associated with Depression is associated with an increase in cardiac riskan increase in cardiac risk
Recurrent depression worsens Recurrent depression worsens cardiac outcomescardiac outcomes
CBT improves mood but does CBT improves mood but does not improve cardiovascular not improve cardiovascular outcomes in depressed outcomes in depressed cardiac patientscardiac patients
SSRIs improves mood and SSRIs improves mood and appears safe in the cardiac appears safe in the cardiac patientpatient
CARDIOLOGY/PRIMARY CARDIOLOGY/PRIMARY CARECARE
20% of patients post MI 20% of patients post MI will have symptoms of will have symptoms of depression depression
Understand the potential Understand the potential mechanisms of how mechanisms of how depression may increase depression may increase the risk for CHD eventsthe risk for CHD events
Treatment of depression Treatment of depression leads to better clinical leads to better clinical outcomes after a cardiac outcomes after a cardiac eventevent
Wulsin, L.R; Harv Rev Psychiatry. March/April 2004Wulsin, L.R; Harv Rev Psychiatry. March/April 2004
MDD is an independent predictor of all cause mortality and CV death after AMI complicated by heart failure
““Insanity: Insanity:
Doing the same thingDoing the same thing over and over again over and over again
and expecting different resultsand expecting different results.”.”
Albert Einstein