Depression And Cardiovascular Disease
has long had a popular link to cardiovascular disease and death.
However, only during the last 15 years scientific evidence supporting
this common wisdom has been available (Glassman et al., 2007a). Since
the early 1990s studies have reported prevalences of major depression
between 17% and 27% in hospitalized patients with coronary artery
disease (CAD)(Rudisch & Nemeroff, 2003).
is becoming clear that the comorbidity of depression and cardiovascular
disease does not occur by chance but the mechanisms responsible for
this relationship is poorly understood. Platelet abnormalities,
autonomic tone, and health behaviors have all been implicated. There
exists also the possibility that depression and vascular disease share
certain vulnerability genes (McCaffery et al., 2006).
it is now apparent that depression aggravates the course of multiple
cardiovascular conditions (Glassman et al., 2007) and has regularly
been shown to lower adherence to prescribed medication and secondary
prevention measures (Glassman et al., 2007b).
randomized controlled trials have evaluated the efficacy of treatments
for major depression in patients with coronary artery disease. New
research helps us to understand which common biological changes are
involved in the already known link between depression and
life-threatening cardiovascular disease.
and cardiovascular disease
observed following acute coronary syndrome (ACS) is common and
associated with an increased risk of mortality. Medically healthy
individuals who suffer from depression are at significantly increased
risk of developing heart attacks and strokes later in life (Glassman et
coronary syndrome is both psychologically and physiologically
stressful, and it is common to attribute depression observed following
ACS to that stress (Glassman et al., 2006)
the Heart rate variability (HRV), a well-recognized measure reflecting
fluctuations in autonomic activity, is an independent predictor of
death. Earlier studies show that, after myocardial infarction, HRV
values increase approximately 50% between 3- and 12-weeks. In post-ACS
patients with depression, improvement in HRV could therefore result
from the pharmacological action of an antidepressant drug, from an
improving mood independent of the drug, or as a result of recovery from
the acute cardiac injury.
treatment among patients with coronary artery disease
adequately controlled trials evaluated whether antidepressant
treatments are either safe or effective in patients with coronary
artery disease (CAD). The largest of these, the Sertraline
Antidepressant Heart Attack Trial (SADHART) (Glassman et al., 2002) was
designed to evaluate the safety and efficacy of sertraline
hydrochloride for treatment of MDD in ACS. No adverse cardiovascular
effects of sertraline treatment were detected, sertraline was both safe
and effective in post-MI depression and observed a reduction in death
and recurrent myocardial infarction. Planned subgroup analyses showed a
clear benefit of sertraline over placebo for patients with recurrent
depression and those with more severe depression.
addition, the Canadian Cardiac Randomized Evaluation of Antidepressant
and Psychotherapy Efficacy, a randomized, controlled, 12-week,
parallel-group trial (CREATE) (Lesperance et al., 2007), was the first
trial specifically designed to evaluate the short-term efficacy and
tolerability of 2 depression treatments in patients with CAD:
citalopram, a first-line SSRI antidepressant and interpersonal
psychotherapy (IPT), a short-term, manual-based psychotherapy focusing
on the social context of depression. The trial documents the efficacy
of citalopram administered in conjunction with weekly clinical
management for major depression among patients with coronary artery
disease and found no evidence of added value of IPT over clinical
management. Similar to the results of SADHART CREATE found the benefits
of SSRIs for patients with CAD to be clearer for recurrent episodes of
major depression than for first episodes.
is a painful state, and it should be treated aggressively when
indicators of benefit are present; major depression following
myocardial infarction is consistently associated with about a 3-fold
increase in cardiac mortality and evidence continues to accumulate
(Glassman et al., 2007b).
depression severely impairs heart rate variability recovery following
an acute coronary event. It is now clear, that depression is also
associated with biological changes involving increased heart rate,
inflammatory response, plasma norepinephrine, platelet reactivity,
absent post-ACS HRV recovery -- all of which is associated with
life-threatening consequences. It also impairs compliance with doctors
advice and health behaviors.
on study results and those of previous trials, the selective
serotonin-reuptake-inhibitors (SSRI) citalopram or sertraline plus
clinical management should be considered as a first-step treatment for
patients with CAD and major depression albeit there is still a clear
need for additional studies evaluating interventions to prevent the
cardiac prognostic impact of depression.
a clinician's point of view, patients with depression after myocardial
infarction, especially those with prior episodes, should be both
carefully watched and aggressively treated, because they are at an
elevated cardiac risk and less likely to get better spontaneousely.
more information on the European College of Neuropsychopharmacology,
Glassman AH. Depression and cardiovascular comorbidity. Dialogues Clin
Glassman AH, Bigger JT, Gaffney M. Heart Rate Variability in Acute
Coronary Syndrome Patients with Major Depression, influence of
Sertraline and Mood Improvement. Arch Gen Psychiatry 2007b;64:9
Glassman AH, Bigger JT, Gaffney M, et al. Onset of major depression
associated with acute coronary syndromes: relationship of onset, major
depressive disorder history, and episodeseverity to sertraline benefit.
Arch Gen Psychiatry 2006;63(3):283-8
Glassman AH, O'Connor CM, Califf RM, et al.; Sertraline Antidepressant
Heart Attack Randomized Trial (SADHEART) Group. Sertraline treatment of
major depression in patients with acute MI or unstable angina. JAMA
Lesperance F, Frasure-Smith N, Koszycki D, et al.; CREATE
Investigators. Effects of citalopram and interpersonal psychotherapy on
depression in patients with coronary artery disease: the Canadian
Cardiac Randomized Evaluation of Antidepressant and Psychotherapy
Efficacy (CREATE) trial. JAMA 2007;297(4):367-79
McCaffery JM, Frasure-Smith N, Dube MP, et al. Common genetic
vulnerability to depressive symptoms and coronary artery disease: a
review and development of candidate genes related to inflammation and
serotonin. Psychosom Med 2006;68(2):187-200
Rudisch B, Nemeroff CB. Epidemiology of comorbid coronary artery
disease and depressi on. Biol Psychiatry 2003;54:227-240.