Depression and cardiovascular disease: recent advances

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Depression and cardiovascular disease recent
advances

• Constantine Lyketsos, MD, MHS
• CoDirector, Division of Geriatric
  Neuropsychiatry
• Professor of Psychiatry and Behavioral Sciences,
  Epidemiology, Mental Health
• School of Medicine
• Bloomberg School of Public Health
• The Johns Hopkins University

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Collaborators

• Hochang Ben Lee, MD
• Assistant Professor of Psychiatry, JHU
• Sherita Hill Golden
• Assistant Professor of Medicine, JHU
• Annette Fitzpatrick, PhD
• Assistant Professor of Epidemiology, U of W
• Moyses Szklo, MD
• Professor of Epidemiology, JHU
• Multi-Ethnic Study of Atherosclerosis

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Overview

• Depression in patients with CVD
• Effect of depression on CVD outcomes
• Depression as a risk factor for CVD
• Treatment of depression in CVD
• Reversal of adverse CVD outcomes?
• The future understanding mechanism
• The MESA Depression-Cognition Study

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Definitions

• Depression heterogeneous
• DSM-IV major or minor depression
• In some cases defined by scores above a scale
  cut-off, typically the BDI or CES-D
• Other important constructs e.g., depression
  without sadness, anhedonia
• CVD Disease of blood vessels with coronary and
  cerebrovascular syndromes, such as MI, CVA
• CHD coronary heart disease
• CVA cerebrovascular accident

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Heart disease

• One month after myocardial infarction
• Major depression 15
• Minor depression 30
• Congestive heart failure
• Major depression 14
• Minor depression 20

Frasure-Smith, Lesperance and collaborators
several publications
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Stroke

• First month after stroke
• Major depression 18
• Minor depression 32
• Anterior, right hemisphere stroke 67
• Over the first year after stroke
• Annual attack rate about 60

Robinson, Morris and collaborators several
publications
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Domains of impact

• Intrinsic to being a psychiatric case
• Mental suffering
• Dangerousness
• Frailty (e.g., weight loss, deconditioning)
• Aggression
• Suicide
• Functional outcomes
• Medical outcomes of the associated disease

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Heart disease

• Depression increases risk of heart disease 2-3x
• After a first myocardial infarction
• Major depression leads to 4x increase of death
• Congestive heart failure
• Major depression leads to 3x increased
  readmission
• Major depression leads to 2.2x increased
  mortality
• Post-CABG (next slide)

Frausre-Smitn, Lesperance and collaborators
several publications
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Depression (1m), outcomes (5y)
McKhann et al, Lancet 2000, Borowicz et al,
Psychosomatics, 2002
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Recovery in functioning after stroke

p lt .01
Robinson and collaborators several publications
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Depression as a risk factor for CHD
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How does treatment affect medical outcomes in CVD?
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Benefit from treating depression?

• Montreal Heart Attack Readjustment Trial (M-HART)
• women receiving nonpharmacologic anxiety-reducing
  intervention after MI more likely to die (RR
  1.39)
• Enhancing Recovery in Coronary Heat Disease
  (ENRICHD)
• psychotherapy for depression did not improve
  survival post-MI
• SADHART study (Sertraline Antidepressant Heart
  Attack Randomized Trial)
• no decrease in mortality with sertraline
  treatment
• Myocardial Infarction and Depression Intervention
  Trial (MIND-IT) underway in the Netherlands
• compares mirtazapine, citalopram, and placebo in
  reducing post-MI mortality among depressed
  persons

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Stroke probability of survival for depressed
patients

P .004
Robinson, et al AJP, 2003
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What is going on?

• The association does not exist
• Depression is indicator of more severe CVD
• Treating depression not expected to affect CVD
• Depression and CVD have similar causes
• Treating one does not affect the other, unless
  the cause is treated
• Depression is heterogeneous
• Understanding mechanisms linking depression (OR
  subtypes of depression) with CVD should produce
  better targets for therapy

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The future confirm the association and what is
the mechanism?

• Biological effects of depression
• Heart rate variability (increased)
• Endothelial reactivity (decreased)
• Coagulation (pro-coagulant)
• Inflammation (pro-inflammatory)
• Cortisolemia
• Behavioral effects of depression
• Co-morbid smoking, drinking
• Less physical activity
• Worse diet
• Worse adherence with CVD treatments

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DEPRESSION

• Biological
• e.g., inflammatory

Plaque formation
CARDIOVASCULAR
Behavioral smoking, diet, physical activity
Obesity
CONFOUNDERS
Obesity
Socioeconomic status Gender Race, ethnicity
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The MESA Study

• 6,814 adults between the ages of 45 and 84
• 38 Caucasians, 28 African-Americans, 22
  Hispanics, and 12 Chinese
• NO clinical CVD at baseline
• Followed every two years in clinical examinations
• Completed 2, in process of 3, starting 4 fall 05
• Depression assessed every time on CES-D
• Window into heterogeneity
• Total score, severe depression, DSM-IV
  approximation, individual items

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MESA biological assessments

• Coronary Calcium on CT
• Magnetic Resonance Imaging (MRI) of the heart and
  carotid arteries
• Enhanced gray-scale and Doppler ultrasound of
  carotid arteries
• Flow-mediated brachial vasodilation
• Arterial wave form tonometry
• Electrocardiogram (ECG)

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MESA other assessments

• Laboratory determinations of key blood and urine
  variables
• Inflammation (e.g., CRP), coagulability, lipids,
  oxidative, insulin resistance
• DNA storage, genetic analyses
• Anthropometry
• Ankle/brachial blood pressure index
• Blood Pressure
• CLINICAL EVENT SURVEILLANCE

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MESA behavioral assessments

• Alcohol intake
• Smoking
• Dietary assessment
• Physical and other leisure activity

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Initial cross-sectional findings MESA
examination 1

• Depression associated with
• Requiring mediations for diabetes
• OR 1.30 (1.03-1.64)
• Ankle brachial index 0.9
• OR 1.51 (1.05-2.18)
• Smoking currently
• OR 1.42 (1.15-1.76)
• Maybe with
• CT coronary calcium
• OR 1.31 (0.95-1.80)
• High blood pressure
• OR 1.15 (0.98-1.34)

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Next steps

• Analyses of existing MESA data in process
• Focus on depression and subclinical CVD
• Longitudinal, testing hypotheses, models
• Accumulating CVD events (e.g., MI, CVA)
• Link depression to clinical CVD
• Seeking funding to look at depression, cognition,
  subclinical, and clinical CVD relationship

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Conclusions

• Depression is linked closely to CVD
• Associated with increased risk for AND worse CVD
  outcomes after onset
• Depression reduction by current means does not
  seem to affect CVD outcomes
• Need better understanding of the linking
  mechanisms in the context of the heterogeneity of
  depression

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Thank you!Eucaristw!