Coronary Heart Disease

1
Coronary Heart Disease DepressionThe
Bi-Directional Relationship

• Madeleine Lloyd MS, RN, FNP, MHNP
• Ana Mola MA, RN, ANP

2
Global 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 1990-2020Global Burden
  Disease Study Lancet May 1997 vol. 349, pp
  1498-1504

3
(No Transcript)
4
(No Transcript)
5
CVD Mortality in US Women Is Not Declining
494,000
434,000
NCEP ATP II
NCEP ATP III
NCEP ATP I
AHA. Heart Disease and Stroke Statistics2005
Update. Expert Panel on Detection, Evaluation,
and Treatment of High Blood Cholesterol in
Adults. JAMA. 20012852486-2497.
6
Global Burden of Disease
MEN
WOMEN
WHO 2002
7
(No Transcript)
8
Hypothalamic-Pituitary-Adrenal (HPA) axis in
depression
9
(No Transcript)
10
Endothelium-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.
1993362801-809.
11
Atherosclerosis is an Inflammatory Disease LDL
pro-inflammatory HDL anti-inflammatory
Vessel Lumen-Teflon Resistent
Monocyte
LDL-small dense particles
Endothelium
Adhesion Modules-increase monocytes adherence
LDL
HDL InhibitOxidationof LDL
Cytokines
oxidized LDL
Foam Cell-increase ANGIOTENSIN II, PAI,
-pro-thrombotic state decrease NO
Macrophages engulf LDL
HDL Promote Cholesterol Efflux
Mackness MI et al. Biochem J 1993294829-834.
12
(No Transcript)
13
Plaque Morphology and Ischemic Impact
Libby, P. et al. Circulation 20051113481-3488
14
Pathophysiology in Motion
15
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
941-962
16
Depression and the Heart

• Recognized in language and literature
• But scientific evidence lacking!
• First credible studies by Meyer Friedman Ray
  Rosenman following WWII
• However, by mid-1970s type As effect vanished

17
Stirling County StudyCardiovascular Deaths
Mortality Rate
1000 Community residents followed 16 yrs
Murphy 1987
18
Depression Associated With Increased Mortality
Post-Myocardial Infarction
Depressed (n 35)
Nondepressed (n 187)
Frasure-Smith N et al. JAMA. 19932701819-1825.
19
Depression and 1-Year Post-Myocardial Infarction
(MI) Cardiac Mortality
N 896
Odds Ratio 3.4 (1.8-6.7) P lt .001
Frasure-Smith N et al. Psychosom Med.
19996118-20.
20
Long-Term Survival Impact of Increasing Levels of
Post-MI Depression
N 896
Lespérance,2000.
21
The Prognostic Impact of Depression
Survival Free of Cardiac Mortality, Cumulative ()
N 896
N 896
Anxiety
Anger
Time After Discharge for MI (Days)
Time After Discharge for MI (Days)
BDI lt 10
Depressed BDIgt10
Survival Free of Cardiac Mortality, Cumulative
()
N 896
N 896
Lower Social Support
Depression
Time After Discharge for MI (Days)
Time After Discharge for MI (Days)
22

SADHART Objectives

• Primary
• To evaluate the safety and efficacy of Sertraline
  as a treatment of depression in patients with AMI
  or unstable angina
• Secondary
• Antidepressant response in more severe subset
  of patients (baseline HAM-D gt 18, 2 prior
  episodes of major depression)
• Improvement in quality of life and functional
  status with Sertraline

23
Efficacy in Post-MI DepressionWeek-24 Responder
Rates for Sertraline vs Placebo
.
24
ENRICHD TRIAL

• 2481 MI patients (33,780 screened)
• 1084 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)3171-3

25
ENRICHD-sub studiesImpact of PE on MDD and LSS

• 982 pt (47) reported they exercise regularly 6
  months after AMI
• Pt who did not exercise tended to be less well
  educated and lower household income and more
  severe CAD
• Exercise was associated with lower levels of
  depression, reduced depressive symptoms and
  increased survival
• Despite failure of CBT to reduced mortality risk
  in this population, exercise maybe a valuable
  addition

Blumenthal 2004 Am. College of Sports
medicine36746-755
26
Myocardial Infarction and Depression-Intervention
Trial (MIND-IT)

• Mirtazapine/Placebo for BDI gt 10 (n190) or care
  as usual (n130)
• 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

27
MIND 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

28
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 6887-93
(2006)
29
Evidence for Depression as an Independent Risk
factor for CAD

• GOOD
• Strength of Association
• Prediction
• Consistency
• Dose-response Effect
• FAIR
• Specificity
• Biological Plausibility

• INSUFFICIENT EVIDENCE
• Cardiac risk reduction in response to treatment
  for depression.

Wulsin, L.R Harv Rev Psychiatry. March/April
2004
30
Criteria for Major Depression
One or the other required

• Depressed mood
• Diminished interest or pleasure
• 5 or more of the following Sx present for gt 2
  weeks
• Fatigue or loss of energy
• Diminished ability to concentrate
• Insomnia or hypersomnia
• Weight loss or weight gain
• Feelings of worthlessness or excessive guilt
• Psychomotor agitation or retardation
• Recurrent thoughts of death or suicidal ideation
  or attempt

31
When to suspect depression in cardiac pts

• Symptoms chronic tiredness, wt loss, insomnia,
  recent onset of irritability or anger
• Impairment reduced social contact, poor ADLs,
  reduced interest, difficulty coping with recent
  losses and stresses
• Medical Management Problems chronic anxiety,
  poor medication compliance or risk factor
  modification

32
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)

33
Meta-Analysis of the Adverse Effect of Depression
on Patient Adherence

• Compared to nondepressed patients, the odds are 3
  times greater that depressed patients would be
  nonadherent with medical treatment recommendations

DiMatteo MR, et al. Arch Intern Med.
2000160(14)2101-2107.
34
Depression Is AssociatedWith ? Smoking
plt0.001 MajorgtNone plt0.01 MinorgtNone N4225
Adjusted for demographics, medical comorbidity,
diabetes severity,diabetes type and duration,
treatment type,HbA1c and clinic. Katon et al,
Diabetes Care, 2004
35
Bi-Directional Conclusions

• PSYCHIATRY
• Depression is associated with an increase in
  cardiac risk
• Recurrent depression worsens cardiac outcomes
• CBT improves mood but does not improve
  cardiovascular outcomes in depressed cardiac
  patients
• SSRIs improves mood and appears safe in the
  cardiac patient

• CARDIOLOGY/PRIMARY CARE
• 20 of patients post MI will have symptoms of
  depression
• Understand the potential mechanisms of how
  depression may increase the risk for CHD events
• Treatment of depression leads to better clinical
  outcomes after a cardiac event

• MDD is an independent predictor of all cause
  mortality and CV death after AMI complicated by
  heart failure

• Wulsin, L.R Harv Rev Psychiatry. March/April
  2004

36

• Insanity
• Doing the same thing
• over and over again
• and expecting different results.