1. Coronary Heart Disease & Depression: The Bi-Directional Relationship
Time is of the essence-
There is death per minute in the U.S. due to CHD.
Why is coronary risk management failing?
What role does the NP play in this process of providing cardiac health.
Are we part of this problem or the solution.
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 :Global Burden Disease Study” Lancet May 1997 vol. 349, pp

5. CVD Mortality in US Women Is Not Declining
494,000
434,000
Despite advances in cardiovascular therapy including thrombolytics, increasing use of antiplatelets, evidence based medicine of lipid-lowering therapy in primary and secondary prevention, third generation of of high tissue affinity ACEI, and selective targeted beta-blockers, their remains a divergent trend in the CVD mortality for trends of males and females.
From the mid 80’s-what are we missing-
Is it that our risk factor estimation models of CHD and/or recognition of subclinical atherosclerosis is not fully sensitive for woman.
The reality of this failure to treat women may be concluded that they are just underdiagnosed, undertreated and and until most recently understudied in the last two decades.
As example, the HERS only 8% of the women with documented CAD had reached ATP II target lipid goals.
Cardiovascular disease deaths: United States 1979–1999
Since the release of the previous NCEP guidelines, instead of a marked fall in cardiovascular mortality in the United States the decline in cardiovascular mortality that predated the guidelines has slowed. In women, there has actually been an increase in incidence of cardiovascular mortality.
Why is it, despite wide dissemination of guidelines that describe highly effective means by which cardiovascular risk can be substantially reduced, that cardiovascular mortality in the United States has not fallen substantially since 1988?
References:
American Heart Association Heart and Stroke Statistical Update. Dallas, Texas: American Heart Association, (available at
Cooper R, Cutler J, Desvigne-Nickens P, et al. Trends and disparities in coronary heart disease, stroke, and other cardiovascular diseases in the United States: Findings of the National Conference on Cardiovascular Disease Prevention. Circulation 2000;102:
Reference
American Heart Association. Heart Disease and Stroke Statistics–2005 Update. Dallas, Tex.: American Heart Association; 2005.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285:
NCEP ATP I
NCEP ATP II
NCEP ATP III
AHA. Heart Disease and Stroke Statistics–2005 Update.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:

6. Global Burden of Disease
MEN
WOMEN
WHO 2002

7. CNS is proposed to play a major role in the etiology of both mood states/depression and CV dysregulation via positive and negative feedback systems. The peripheral nervous system changes are likely mediated by brain mechanisms that can lead to specific cardiac events. Feedback from the CVS to the brain perpetuates the cycle of dysregulation and may also lead to depressive symptoms. The influence of exogenous stressors, either alone or coupled with genetic or experiential predisposition may play a role in the initiation of depression and in the pathogenesis of heart disease.
There is no proven biological mechanisms by which depression contributes to the development or the progression of the pathophysiology of coronary disease but a variety of promising hypotheses has emerged over the past several years.
Aside from the indirect effects of depression –interfering with self-care and exacerbating traditional coronary disease risk factors (behavioral pathway) several neurochemical and neuroendocrine mechanisms and neuro anatomical alterations that have been proposed as specific pathways.
1) Hyperactive Hypothalamus Pituitary Adrenal Axis and Sympathomedullary Activity- in response to the flight or fight response “General Adaptation Syndrome” Selye- the hypothalamic neurons containing corticotropin are stimulated to increase the synthesis and release CRF. These hypothalamic CRF provide stimulating input to several autonomic centers involved in regulating sympathetic activity such as the anterior pituitary which secretes ACTH adrenocorticotropin hormone which signals the adrenal gland to increase the release of catecholamines and cortisol to hyperactivate the SNS. The catecholamines are epinephrine from adrenal medulla and norepinephrine NE from sympathetic nerve terminals and remaining NE from adrenal gland and extra medulla chromaffin cells.
CARDIAC:
The biologiacal plausibility of an hyperactive sympathetic medullary response has been proven to contribute to the development of CVD through the effects of catecholamines upon the Beta adrenergic receptors and NE receptors to increase HR, contractility and activation of platelets.
Increases the shear stress of arterial vessels
induces myocardial ischemia
Decreased HRV which essentially is the act of increasing sympathetic tone which decreases Ventricular threshold for VF- HRV reflects the capacity of the ANS to vary the intervals between consecutive heartbeats (R to R interval the 1st positive deflection of the QRS complex in NSR) according to the hemodynamic fluctuations. It is the homoestasis of the sympathetic and parasympathetic nervous system to alter HR, AV conduction, contractility and vasomotor tone of arterial vessels. Central control of HR is regulated by the hypothalamus, limbic system and brainstem. Neurotransmitters involved in modulating HRV centrally and peripherally are acetycholine, NE, serotonin, and dopamine. There is an increase in HRV in nomral hearts and a decrease HRV in CAD/HF patients. There is a relative increase risk of sudden death after AMI in patients with decreased HRV.
Reduced Baroreflex Sensitivity-arterial baroreceptors are mechanoreceptors located in the aortic arch and carotid sinus which serve to regulate BP by affecting the CO and vasoconstriction. Baroreceptor reflex responds to changes in arterial pressure by altering cardiac parameters such as HR, contractility and vascular tone. Decreased BP maybe restored with increase cardiac rate and contractility initiated by SNS as well as the withdrawal of inhibitory influences on HR contractility exerted by vagal mechanisms. The response to an increase BP involves the activation of the vagal mechanisms to decrease HR, CO, and vascular tone. Decrease BRS may contribute to CV mortality through a reduction in parasympathetic activity as well as increase in sympathetic activity (decrease ventricular threshold which leads to VF during a brief ischemic episode). LaRovere and Bigger 1998, Lancet, found the combo of decreased BRS and decrease HRV were of additional prognostic value in a sample of post MI patients compared to that of either marker alone.
Immune System Dysfunction-pts. with unstable angina have been shown to overexpress monocytes receptors and upregulate the formation of macrophages at sites of plaque rupture and they release substances that promote thrombosis.Specific cytokines interleukin-1 and 6, interferon and TNF influence the release and metabolism of several neurotransmitters that are involved in the sympathetic nerve outflow to the CVS as well as the pathogenesis of of depression.
Modifies the function of circulating platelets increase activation and aggregation for clotting purposes as discussed in the next slide
DEPRESSION:
It has been researched that depressed patients that are medication free have a HPA that is hyperactive with increased CRF concentrations in cerebral spinal fluid. In addition, it has been found that there are increased CRF neurons in the hypothalamus of postmortem tissue of depressed patients. Additionally, with depression the increase in cortisol secretion impairs feedback regulation of plasma cortisol which alters the CRF/ACTH concentrations and perperuates the increase catecholamines.
Furthermore, hypersecretion of NE in major depression and also in hypertension has been documented by increase plasma NE and NE metabolites concentrations because of the increased sympathetic tone possible seen in both co-morbidites.
Decrease HRV has been observed in depressed patients in comparison with non-depressed patients with the theory that they are in sympathetic overdrive decreasing ventricular threshold and increasing VF. HRV has been observed to increase in depressed patients following antidepressant medication treatment and CBT.
Watkins and Grossman 1999 American Heart Journal 1: that there was an association of depressive symptoms with reduced baroreflex sensitivity.
The function of the immune system in depressed patients is complex involving both hyperactivity of certain immune components and hypoactivity of others. MMD is associated with excessive secretion of proinflammatory cytokines interleukin-1, TNF and interferon. Depressed individuals show an increased number of leukocytes-moreover an increased number of phagocytic activity of monocytes differentiating into macrophages releasing these cytokines. Macrophages are known to release ACTH thereby influencing the HPA. In addition, Interleukin-1 produced by the macrophages has a direct effect on the hypothalamus and pituitary leading to subsequent release od CRH and ACTH. It has been found in depressed pts-this alteration is reverswed following successful antidepressant treatment. Depressed individuals show a blunted cell-mediated immune response indicating immunosuppression-decrease number of T-Helper and B cells.
Dysfunction in the HPA axis in depressed patients is mirrored by dysfunction in the SNS. Altered catecholamine release and function of NE, dopamine and increase synthesis of serotonin is evident in depressed individuals.

8. Hypothalamic-Pituitary-Adrenal (HPA) axis in depression
The hypothalamic-pituitary-adrenal (HPA) axis in depression
In depression, the hypothalamic-pituitary-adrenal (HPA) axis is upregulated with a down-regulation of its negative feedback controls. Corticotropin-releasing factor (CRF) is hypersecreted from the hypothalamus and induces the release of adrenocorticotropin hormone (ACTH) from the pituitary. ACTH interacts with receptors on adrenocortical cells and cortisol is released from the adrenal glands; adrenal hypertrophy can also occur. Release of cortisol into the circulation has a number of effects, including elevation of blood glucose. The negative feedback of cortisol to the hypothalamus, pituitary and immune system is impaired. This leads to continual activation of the HPA axis and excess cortisol release. Cortisol receptors become desensitized leading to increased activity of the pro-inflammatory immune mediators and disturbances in neurotransmitter transmission.

9. CNS is proposed to play a major role in the etiology of both mood states/depression and CV dysregulation via positive and negative feedback systems. The peripheral nervous system changes are likely mediated by brain mechanisms that can lead to specific cardiac events. Feedback from the CVS to the brain perpetuates the cycle of dysregulation and may also lead to depressive symptoms. The influence of exogenous stressors, either alone or coupled with genetic or experiential predisposition may play a role in the initiation of depression and in the pathogenesis of heart disease.
There is no proven biological mechanisms by which depression contributes to the development or the progression of the pathophysiology of coronary disease but a variety of promising hypotheses has emerged over the past several years.
Aside from the indirect effects of depression –interfering with self-care and exacerbating traditional coronary disease risk factors (behavioral pathway) several neurochemical and neuroendocrine mechanisms and neuro anatomical alterations that have been proposed as specific pathways.
1) Hyperactive Hypothalamus Pituitary Adrenal Axis and Sympathomedullary Activity- in response to the flight or fight response “General Adaptation Syndrome” Selye- the hypothalamic neurons containing corticotropin are stimulated to increase the synthesis and release CRF. These hypothalamic CRF provide stimulating input to several autonomic centers involved in regulating sympathetic activity such as the anterior pituitary which secretes ACTH adrenocorticotropin hormone which signals the adrenal gland to increase the release of catecholamines and cortisol to hyperactivate the SNS. The catecholamines are epinephrine from adrenal medulla and norepinephrine NE from sympathetic nerve terminals and remaining NE from adrenal gland and extra medulla chromaffin cells.
CARDIAC:
The biologiacal plausibility of an hyperactive sympathetic medullary response has been proven to contribute to the development of CVD through the effects of catecholamines upon the Beta adrenergic receptors and NE receptors to increase HR, contractility and activation of platelets.
Increases the shear stress of arterial vessels
induces myocardial ischemia
Decreased HRV which essentially is the act of increasing sympathetic tone which decreases Ventricular threshold for VF- HRV reflects the capacity of the ANS to vary the intervals between consecutive heartbeats (R to R interval the 1st positive deflection of the QRS complex in NSR) according to the hemodynamic fluctuations. It is the homoestasis of the sympathetic and parasympathetic nervous system to alter HR, AV conduction, contractility and vasomotor tone of arterial vessels. Central control of HR is regulated by the hypothalamus, limbic system and brainstem. Neurotransmitters involved in modulating HRV centrally and peripherally are acetycholine, NE, serotonin, and dopamine. There is an increase in HRV in nomral hearts and a decrease HRV in CAD/HF patients. There is a relative increase risk of sudden death after AMI in patients with decreased HRV.
Reduced Baroreflex Sensitivity-arterial baroreceptors are mechanoreceptors located in the aortic arch and carotid sinus which serve to regulate BP by affecting the CO and vasoconstriction. Baroreceptor reflex responds to changes in arterial pressure by altering cardiac parameters such as HR, contractility and vascular tone. Decreased BP maybe restored with increase cardiac rate and contractility initiated by SNS as well as the withdrawal of inhibitory influences on HR contractility exerted by vagal mechanisms. The response to an increase BP involves the activation of the vagal mechanisms to decrease HR, CO, and vascular tone. Decrease BRS may contribute to CV mortality through a reduction in parasympathetic activity as well as increase in sympathetic activity (decrease ventricular threshold which leads to VF during a brief ischemic episode). LaRovere and Bigger 1998, Lancet, found the combo of decreased BRS and decrease HRV were of additional prognostic value in a sample of post MI patients compared to that of either marker alone.
Immune System Dysfunction-pts. with unstable angina have been shown to overexpress monocytes receptors and upregulate the formation of macrophages at sites of plaque rupture and they release substances that promote thrombosis.Specific cytokines interleukin-1 and 6, interferon and TNF influence the release and metabolism of several neurotransmitters that are involved in the sympathetic nerve outflow to the CVS as well as the pathogenesis of of depression.
Modifies the function of circulating platelets increase activation and aggregation for clotting purposes as discussed in the next slide
DEPRESSION:
It has been researched that depressed patients that are medication free have a HPA that is hyperactive with increased CRF concentrations in cerebral spinal fluid. In addition, it has been found that there are increased CRF neurons in the hypothalamus of postmortem tissue of depressed patients. Additionally, with depression the increase in cortisol secretion impairs feedback regulation of plasma cortisol which alters the CRF/ACTH concentrations and perperuates the increase catecholamines.
Furthermore, hypersecretion of NE in major depression and also in hypertension has been documented by increase plasma NE and NE metabolites concentrations because of the increased sympathetic tone possible seen in both co-morbidites.
Decrease HRV has been observed in depressed patients in comparison with non-depressed patients with the theory that they are in sympathetic overdrive decreasing ventricular threshold and increasing VF. HRV has been observed to increase in depressed patients following antidepressant medication treatment and CBT.
Watkins and Grossman 1999 American Heart Journal 1: that there was an association of depressive symptoms with reduced baroreflex sensitivity.
The function of the immune system in depressed patients is complex involving both hyperactivity of certain immune components and hypoactivity of others. MMD is associated with excessive secretion of proinflammatory cytokines interleukin-1, TNF and interferon. Depressed individuals show an increased number of leukocytes-moreover an increased number of phagocytic activity of monocytes differentiating into macrophages releasing these cytokines. Macrophages are known to release ACTH thereby influencing the HPA. In addition, Interleukin-1 produced by the macrophages has a direct effect on the hypothalamus and pituitary leading to subsequent release od CRH and ACTH. It has been found in depressed pts-this alteration is reverswed following successful antidepressant treatment. Depressed individuals show a blunted cell-mediated immune response indicating immunosuppression-decrease number of T-Helper and B cells.
Dysfunction in the HPA axis in depressed patients is mirrored by dysfunction in the SNS. Altered catecholamine release and function of NE, dopamine and increase synthesis of serotonin is evident in depressed individuals.

10. Endothelium-Teflon Resistant
2.02
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: ;362:

11. Atherosclerosis is an Inflammatory Disease
LDL pro-inflammatory & HDL anti-inflammatory
Vessel Lumen-Teflon Resistent
Monocyte
LDL-small dense particles
Adhesion Modules-increase monocytes adherence
Endothelium
LDL
HDL Inhibit Oxidation of LDL
Cytokines
oxidized LDL
HDL inhibit the oxidative modification of LDL
HDL has protective effects in addition to promoting cholesterol efflux. One of the best known of these is the ability to inhibit the oxidation of LDL. To the extent that LDL oxidation is an important step in the development of the inflammatory process, this property of HDL is clearly anti-inflammatory.
Reference:
Mackness MI, Abbott C, Arrol S, Durrington PN. The role of high-density lipoprotein and lipid-soluble antioxidant vitamins in inhibiting low-density lipoprotein oxidation. Biochem J 1993;294:
Foam Cell-increase ANGIOTENSIN II, PAI, -pro-thrombotic state & decrease NO
Macrophages engulf LDL
HDL Promote Cholesterol Efflux
Mackness MI et al. Biochem J 1993;294:

13. Plaque Morphology and Ischemic Impact
Libby, P. et al. Circulation 2005;111:

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 :

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-1970’s type A’s effect vanished
In 1937, Malzberg[1] described for the first time that depression is related to cardiac mortality. After that, it took several decades before a growing number of both population and clinical studies confirmed this relationship and tried to elucidate it. Today, the phenomenon is still far from unraveled. In prospective population studies, subjects with depressive symptoms were found to have an increased risk for coronary artery disease (CAD), myocardial infarction (MI), and cardiac death.[2] [5] In patients already known to have cardiac disease, depression proved to predict poor cardiac outcome.[6] [9] For example, post-MI depression (either notable symptoms or a depressive disorder) was found to be associated with a 3- to 8-fold increase in the risk of cardiac death for as long as 5 years after MI[10] [14] and a 2- to 4-fold increase in the risk of arrhythmic events.[11] [15]
Estimates of the prevalence of depressive disorder in patients hospitalized for MI range from 16% to 19%.[12] [16] [17] Another approximately 20% of the patients show some symptoms of depression during hospitalization but do not fulfill the more stringent criteria for a psychiatric diagnosis of “depressive disorder” (eg, presence of minimum number of symptoms, including key symptoms, for at least 2 weeks, almost every day, most of the day, and abnormal for the individual). However, onset of an episode of depressive disorder after discharge from the hospital has been shown to be common, especially within the first 6 months after MI.[16] [18] [19] Together, it has been estimated that approximately one third of the patients experience an episode of depressive disorder in the first year after their MI.[

17. Stirling County Study Cardiovascular Deaths
Mortality Rate
A 16-year prospective study of a general population sample indicates that those who had reported a depression and/or anxiety disorder at baseline experienced 1.5 times the number of deaths expected on the basis of rates for a large reference population. As part of the Stirling County Study (Canada), the information was gathered from 1003 adults through structured interviews and was analyzed by means of a diagnostic computer program. The risk for mortality was assessed using external and internal standards, controlling for the effects of age and sex as well as for the presence of self-reported physical disorders at baseline. Increased risk was found to be significantly associated with affective but not physical disorders and with depression but not generalized anxiety. When this evidence about mortality was combined with information about subsequent psychiatric morbidity among survivors, 82% of those who were depressed at baseline had a poor outcome.
1000 Community residents followed 16 yrs
Murphy 1987

18. Depression Associated With Increased Mortality Post-Myocardial Infarction
Depressed (n = 35)
Nondepressed (n = 187)
The impact of depression on post-myocardial infarction (MI) cardiac mortality was assessed prospectively among 222 patients in a large, university hospital over the first 6 months after discharge.
Consenting patients were enrolled who met the established criteria for MI between August 1991 and July 1992 and survived to be discharged from the hospital. Patients were followed for up for 6 months. The mean age was 60 years (range, 24 to 88 years), and 78% were male.
At approximately 7 days post-MI, patients were interviewed in the hospital by a research assistant using the National Institute of Mental Health Diagnostic Interview Schedule (DIS), which provided sufficient data for a diagnosis of depression according to DSM-III-R criteria. Based on the DIS results, 35 patients (16%) were diagnosed with major depressive disorder. Only 3 patients were prescribed antidepressant therapy.
A total of 12 patients had died at 6 months, including 6 depressed patients (17%) and 6 nondepressed patients (3%). All deaths were due to cardiac causes.
The Kaplan-Meier cumulative mortality curve for depressed and nondepressed patients is depicted in the graph. Major depression was a significant predictor of mortality at 6 months (Cox model hazard ratio, 5.74; 95% confidence interval, 4.61 to 6.87; P=0.0006).
The increase in risk among depressed patients remained after controlling for other clinical variables such as left ventricular dysfunction (Killip class) and previous MI.
Source:
Frasure-Smith N, et al. JAMA. 1993;270:
Frasure-Smith N et al. JAMA. 1993;270:

19. Depression and 1-Year Post-Myocardial Infarction (MI) Cardiac Mortality
Odds Ratio = 3.4 ( )
P < .001
Frasure-Smith N et al. Psychosom Med. 1999;61:18-20.

20. Long-Term Survival Impact of Increasing Levels of Post-MI Depression
Lespérance,2000.

21. The Prognostic Impact of Depression
1460
365
730
1095
100%
90%
80%
1460
365
730
1095
100%
90%
80%
Survival Free of Cardiac Mortality, Cumulative (%)
N = 896
N = 896
Anxiety
Anger
Time After Discharge for MI (Days)
Time After Discharge for MI (Days)
1460
365
730
1095
100%
90%
80%
BDI < 10
1460
365
730
1095
100%
90%
80%
2003 (Archives of General Psychiatry) Study published by Nancy Frasure-Smith and Francois Lesperance exploring depression and other psychological risks such as anxiety, anger, social support as a prediction of long term cardiac related mortality following MI independently of each other over 5 yrs. MDD remains a significant predictor for cardiac disease severity.
Social isolation and low socioecomonic status are also related to CAD progression but the # of studies and strength of association for each is smaller than the evidence for depression. Though anxiety symptoms have attracked much research, but with equivocal results, the relationship between any specific anxiety DO such as OCD and CAD is less well studied and less robust than MDD and CAD.
Depressed BDI>10
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 > 18, 2 prior episodes of major depression)
Improvement in quality of life and functional status with Sertraline
Outcome Variables
Primary
Change from baseline in resting left ventricular ejection fraction by radionuclide angiography
Secondary
Pulse, BP, ECG, and Holter recording
Treatment-emergent CEC-adjudicated events, including rehospitalization, reinfarction, death
Antidepressant response in “more severe” subset of patients (baseline HAM-D > 18, 2 prior episodes of major depression)
QOL and functional status assessed using LES-Q and Medical Outcomes Study SF-35

23. Efficacy in Post-MI Depression: Week-24 Responder Rates for Sertraline vs Placebo
Sertraline was effective in treating recurrent MDD in pts either with an AMI or an episode of unstable angina.
Zoloft achieved statistical significance vs placebo in the recurrent MDD group.
Also QOL measures greatly improved in this sub group on zoloft .

24. Berkman, L.F., et al. JAMA 2003 289 (23):3171-3
ENRICHD TRIAL
2481 MI patients (33,780 screened)
1084 Women Men 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
Enhancing recovery in Coronary Heart Disease Pts.
Landmark trial to bring together different professions.
This study had the largest number of depressed pts and one of the longest f/u periods of any prognostic study of depression in post AMI
First large multicenter clinical trial to investigate the effects of psychosocial intervention on reinfarction and death in pts with AMI who are depressed or lack social support. CBT based on BECKs CBT for depression. 3 individual sessions then group for 6 months or 12 months if drug augmentation was needed. CBT was started at a median of 17days post MI for a median of 11 sesions throughout 6 months.
Pt was seen by psychiatrist if HAM-D >/= 24 for pharmacotherapy (zoloft initiated at 50mg/day and adjusted to 200mg if needed) or had < 50% reduction in BECKs Depression inventory after 5 weeks.
Conclusion: The intervention did not increase event-free survival. CBT improved depression and social isolation.
There was only a small between group difference in depression outcomes so that still does not negate the importance of depression as a risk factor for post MI.
H.R. = hazard ratio (survival ratio, form of relative risk, )
Berkman, L.F., et al. JAMA (23):3171-3

25. ENRICHD-sub studies: Impact 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
LSS= low social support after MI and 6 months later.
Predominantly caucasian and with mean age 60yr.
Followed for 4yrs the proprtion of deaths were ½ that of non exercises.
Blumenthal: 2004 Am. College of Sports medicine36:

26. 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

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
BDI aadministered during hospitalisation at 3,6,9 and 12 months using scaore >= 10 as +ve
4 groups of LVEF <30, 30-45, >60
Younger age and LV dsyfunction are 2 predictors of depression staus in <3months post MI upto 1 yr.
Evidence for post MI dre

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
All pt with CAD have had a previous MI or > 50% blockage in at least 1 major coronary artery
IPT minute session on a weekly basis
Frassure-Smith, Psychosomatic Medicine 68:87-93 (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.
Medical epidemiology has established scientifically rigorous criteria for assessing risk factor status.
Wulsin used the same criteria as smoking, HTN, Hyperlipidemia, obesity, DM
Strength of Association: 47 original articles reported a measure of association between MDD and CAD, duration of follow up 4-40yrs.
Prediction: The overall risk for the development of CAD in depressed subjects was strong evidence with statistically significant.
Consistency: causal interpretation is enhanced when studies produce similar results esp if various populations are studied, methods and time periods. From 40 original studies only 5 were –ve. Over the past 3 decades, middle-aged and elderly populations in psych, medical and community samples in Europe and Nth America for all phases of CAD its development progression and mortality the evidence is strong.
Specificity: how specific are the measures and the associations. Does depression correlate with depression more strongly than with other psychosocial variables. Of the 47 report 32% used structured interview where as 53% measured depression using self report measures only. Also it has yet to be measured which aspects of depression create the greatest risk for CAD.
Biological: variety of promising hypothesis as Ana has shown. over the past 5 yrs. But none have been proven to link the clinical course of these 2 DO.
Response to Tx: ?does tx MDD reduce risk for CAD or progression. Enrichd trial had only a modest effect
SADHART: 20% few adverse CV events than placbo but not stat significant. INCOMPLETE
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 > 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
Major depression: >/= 5 depressive symptoms for >/= 2 weeks
Minor MDD: 2 to 4 depressive symptoms for ./= 2 weeks
Dysthymia: 3 or 4 dysthymic symptoms including depressed mood, causing significant impairment in social, occupational or ADLs.
Adjustment DO: (with mixed anxiety and MDD) (occurs within 3 months but no longer than 6 months post the stressor.
The primary risk factors for major depressive disorder include:  Female gender, history of depressive illness in first degree relatives, Prior episodes of major depression. The following five-step sequence can help determine whether depression is present or if another illness could be causing the patient's symptoms:
1. Ask closed-ended questions about the nine diagnostic criteria for depression (see above).
2. Ask about alcohol and substance abuse and the use of other medications that may be associated with depressive symptoms.
3. Conduct a medical review of systems that may elicit the presence of medical disorders that are biologically caused or are commonly associated with depressive symptoms.
4. Ask about other psychiatric conditions such as anxiety disorder; when physical symptoms are present, pay particular attention to the course and frequency.
5. Exclude alternative causes (1 through 4, above) for depressive symptoms or syndromes to diagnose a primary mood disorder. Limited laboratory testing that may help rule out associated disorders includes measurement of thyroid function (TSH), electrolytes, folate, vitamin B12, and an electrocardiogram.
It also may be useful to ask about the following potential precipitants of depression:
    Recent losses such as a move from a familiar neighborhood, divorce, death of parents, loss of health, or loss of trust in an organization (eg, abrupt changes in employment).  Separation from important relationships or environments, which may precipitate a depressive episode in a person with an underlying biological tendency.     Stressors such as the traumas of immigration, cultural upheaval, violence, and sudden economic shifts. The depression of trauma (post-traumatic stress disorder) often involves poor sleep, nightmares, vigilance, flashbacks, and startle reactions, which differentiate this condition from major depression.  Developmental events such as school graduations and children leaving home, retirement issues, diminishing physical capacities, and life events associated with diminished self esteem.
    Medical illnesses that bring about a sense of loss due to associated decreased energy and diminished physical capacity, or illnesses that are causes of depression     Substance abuse, which can be both an attempt to self-treat depressive symptoms as well as a cause of depression.  Socioeconomic factors such as lack of employment, poor prospects for financial self support, and broken homes. Physicians should also inquire about a history of depression in siblings and parents. Patients may reveal a previously undisclosed uncle, parent, or sibling with a suicide attempt or hospitalization. This can open the door to a discussion of the patient's own anxiety about their vulnerability to depression.
Depression is one of the most common psychiatric disorders associated with suicide. The clinician may worry that asking about suicide will initiate suicidal thoughts or actions, but there is no data to support this concern. The evaluation of a patient who may be suicidal includes an assessment of ideation, plan, and intent. Components of an evaluation for suicide risk include the following:
    Presence of suicidal or homicidal ideation, intent, or plan    Access to means for suicide and the lethality of those means     Presence of psychotic symptoms, command hallucinations, or severe anxiety     Presence of alcohol or substance use     History and seriousness of previous attempts     Family history of or recent exposure to suicide

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
Key points to remember in managing depression in cardiac pts.
Depression is a chronic illness
Minimal support and education should always accompany Rx for antidepressants.
3.Start low and slow
Sick leave is important
get family involved and enc social interaction
Promote CR
Smoking cessation

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)
There is little evidence to recommend one screening method over another, so clinicians can choose the method that best fits their personal preference, the patient population served, and the practice setting.
Self-report measures of depression though sensitive to clincal depresssion are, in general, measures of distress and not specific to depression. The most specific measures of depression are those of structured diagnostic interview.
All positive screening tests should trigger full diagnostic interviews that use standard diagnostic criteria to determine the presence or absence of specific depressive disorders, such as major depression and/or dysthymia [4]. The severity of depression and comorbid psychological problems (eg, anxiety, panic attacks, or substance abuse) should be addressed.Several depression screening instruments are available; most instruments have relatively good sensitivity (80 percent to 90 percent) but only fair specificity (70 percent to 85 percent) [2]. Most instruments are easy to use and can be administered in less than five minutes. Shorter screening tests, including simply asking questions about depressed mood and anhedonia, appear to detect a majority of depressed patients.
BDI, CES-D and Zung were developed specifically to identify depression. They include similar numbers of questions and rank symptom severity or classifying frequesncy of symptoms. These 3 are the most thoroughly evaluated in primary care and be used to monitor response to Tx
Single Question: for PCP who wants to screen for MDD that could be asked during a prevention evalaution or HM visit or might be asked in response to a pt’s –ve trigger.

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. 2000;160(14):

34. Depression Is Associated With ↑% Smoking
p<0.001; Major>None
p<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

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.”
Albert Einstein