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Coronary Heart Disease & Depression : The Bi-Directional Relationship Madeleine Lloyd MS, RN, FNP, MHNP Ana Mola MA, RN, ANP.

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Presentation on theme: "Coronary Heart Disease & Depression : The Bi-Directional Relationship Madeleine Lloyd MS, RN, FNP, MHNP Ana Mola MA, RN, ANP."— Presentation transcript:

1 Coronary Heart Disease & Depression : The 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 1990-2020:Global Burden Disease Study Lancet May 1997 vol. 349, pp 1498-1504

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5 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 IINCEP ATP IIINCEP ATP I 434,000 494,000

6 Global Burden of Disease WHO 2002 MENWOMEN

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8 Hypothalamic-Pituitary-Adrenal (HPA) axis in depression

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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. 1993;362:801-809.

11 LDL-small dense particles LDL Mackness MI et al. Biochem J 1993;294:829-834. Endothelium Vessel Lumen-Teflon Resistent Monocyte oxidized LDL Macrophages engulf LDL Adhesion Modules- increase monocytes adherence Cytokines Atherosclerosis is an Inflammatory Disease LDL pro-inflammatory & HDL anti-inflammatory Foam Cell-increase ANGIOTENSIN II, PAI, -pro- thrombotic state & decrease NO HDL Promote Cholesterol Efflux HDL Inhibit Oxidation of LDL

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13 Libby, P. et al. Circulation 2005;111:3481-3488 Plaque Morphology and Ischemic Impact

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 Study Cardiovascular Deaths Mortality Rate Murphy 1987 1000 Community residents followed 16 yrs

18 Frasure-Smith N et al. JAMA. 1993;270:1819-1825. Depressed (n = 35) Nondepressed (n = 187) Depression Associated With Increased Mortality Post-Myocardial Infarction

19 Frasure-Smith N et al. Psychosom Med. 1999;61:18-20. Depression and 1-Year Post-Myocardial Infarction (MI) Cardiac Mortality N = 896 Odds Ratio = 3.4 (1.8-6.7) P <.001

20 Lespérance,2000. N = 896 Long-Term Survival Impact of Increasing Levels of Post-MI Depression

21 N = 896 Lower Social SupportDepression 146003657301095 100% 90% 80% 14600365730 1095 100% 90% 80% Time After Discharge for MI (Days) Survival Free of Cardiac Mortality, Cumulative (%) AnxietyAnger 146003657301095 100% 90% 80% 146003657301095 100% 90% 80% Survival Free of Cardiac Mortality, Cumulative (%) Time After Discharge for MI (Days) The Prognostic Impact of Depression N = 896 BDI < 10 Depressed BDI>10

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

23 Efficacy in Post-MI Depression: Week-24 Responder Rates for Sertraline vs Placebo.

24 ENRICHD TRIAL 2481 MI patients (33,780 screened) 2481 MI patients (33,780 screened) 1084 Women 1397 Men 8 centers 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 ä Berkman, L.F., et al. JAMA 2003 289 (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 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 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 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 Despite failure of CBT to reduced mortality risk in this population, exercise maybe a valuable addition Blumenthal: 2004 Am. College of Sports medicine36:746-755

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

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 68:87-93 (2006)

29 Evidence for Depression as an Independent Risk factor for CAD GOOD 1. Strength of Association 2. Prediction 3. Consistency 4. Dose-response Effect FAIR 5. Specificity 6. Biological Plausibility INSUFFICIENT EVIDENCE 7. Cardiac risk reduction in response to treatment for depression. Wulsin, L.R; Harv Rev Psychiatry. March/April 2004

30 Criteria for Major Depression Depressed mood Depressed mood Diminished interest or pleasure Diminished 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 energy Fatigue or loss of energy Diminished ability to concentrate Diminished ability to concentrate Insomnia or hypersomnia Insomnia or hypersomnia Weight loss or weight gain Weight loss or weight gain Feelings of worthlessness or excessive guilt Feelings of worthlessness or excessive guilt Psychomotor agitation or retardation Psychomotor agitation or retardation Recurrent thoughts of death or suicidal ideation or attempt Recurrent thoughts of death or suicidal ideation or attempt One or the other required

31 When to suspect depression in cardiac pts Symptoms: chronic tiredness, wt loss, insomnia, recent onset of irritability or anger 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 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 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 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):2101-2107.

34 Depression Is Associated With % Smoking p None p 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 Wulsin, 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

36 Insanity: Insanity: Doing the same thing Doing the same thing over and over again over and over again and expecting different results. and expecting different results. Albert Einstein


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