E.Mahfouz, CardioEgypt 2008

By

Essam Mahfouz, MDProfessor of Cardiology, Mansoura

University

Depression & Cardiovascular Disease

Agenda

Introduction

Epidemiology

Definitions and diagnosis

Depression and CAD

Pathophysiologic mechanisms

Depression and HF

Unresolved issues

Take home messages

Introduction

A figurative interdependence between the heart and sadness has long existed in language and in literature.

In 1628, English physician William Harvey noted “every affection of the mind that is attended either with pain or pleasure, hope or fear, is the cause of an agitation whose influence extends to the heart”

1970s-epidemiologists start to associate/correlate heart disease and depression.

Definitions • Depression is a mood disturbance

characterized by feelings of sadness, despair, and loss of interest or pleasure in activities. It include: • Major depressive episode • Dysthymia

• The key features of the depressive disorders are:• Low mood;• Reduced energy; and• Loss of interest or enjoyment

Loss ofInterest

Guilty Thoughts

Reduced Self

Confidence

Poor Concent.

Sleep &Appetite Disturb.

Pessimism

Suicide

ReducedEnergy

Lowmood

Keyfeatures ofdepression

SIGECAPS

E.Mahfouz, CardioEgypt 2008

Prevalence of depression in clinical practice

Epidemiology • Major depression strikes 10-15% of

adults, affecting all racial, ethnic, age, and socioeconomic groups. It's twice as common in women as in men and is especially prevalent among adolescents.

• Depression is associating 20-30% of patients with cardiac disease

• Recently new risk factors for CAD have been identified, among them emotional distress and depression. With 1.5-2 fold increase in CAD

Depression & CADRelative risk for myocardial infarction in patients with depressive symptoms versus non-depressive patients ranged from 1.5 to 4.5The prevalence of depression was about 17% in patients with stable CAD and about 25% in patient with acute MI while minor depressive symptoms ranged from 27 to 65 %Depressed patients with stable coronary disease are much more likely to perceive greater coronary symptom burden and physical limitation compared to non-depressed coronary patients

Depression & CADDepressed patients with ACS was shown to have poor quality of life and functional disability than non depressed patient

In patients with CABG, it has been shown that depression diagnosed before surgery was related to higher hospital re-admission rates and was an independent risk factor for cardiac events after surgery

Depression & CADDepression is now a recognized independent risk factor of CAD.Patients with MDD and type 2 DM have 30% increased risk of AMI but patients with both disorders have 82% risk ( Scherrer et al diabetic care 2011)

Post-MI patients with a depressive disorder or self-reported depressive symptoms carry a 2.0- to 2.5 fold increased relative risk of new CV events and cardiac mortality*However, why depression is a risk factor for poor prognosis is unclear

Prognostic Effect of Post-MI Depression

de Jonge et al JACC,2006

Lesperance et al, Circulation 2002;105:1049–53

Long-term survival after MI in relation to Beck Depression Inventory Score during hospitalization

Mechanisms of CAD in depression

• Hypothalamic-adrenocortical and sympatho-adrenal effects• Cortisol.• Blood glucose.• Cholesterol.• Free fatty acids.• Insulin.

• Hematological effects• Plasma fibrinogen.• Platelets aggregation.• Platelet factor 4.• B-Thromboglobulin.

• Cardiac autonomic dysregulation• Arrhythmias ( sinus tachycardia to SCD)• Decreased heart rate variability.• Increased Q-T dispersion

• Cardiac and vascular effects• Carotid-intima media thickness.• Endothelial dysfunction.• Left ventricular mass.

Mechanisms of CAD in depression

• Inflammatory markers• Increased CRP• Other markers ( IL6, TNF, adhesion molecules) show controversial data

• Increased Abs to certain viruses e.g. Epstein Barr, CMV& HS

• Behavioral mechanisms:• Delay in seeking medical treatment• Failure of risk factors modifications:

• Smoking cessation• Control of DM

• Poor adherence to medications

Mechanisms of CAD in depression

• Genetic factors• Depression and CHD may be different phenotypic

expressions of the same genetic substrates• Depression may be genetically related to other CAD

risk factors• Depression and vascular disease may share certain

vulnerability genes

Mechanisms of CAD in depression

Relationship between Depression & CVD

Depression in CAD• Most are never diagnosed• Even when diagnosed, the

treatment options are unclear• No evidence-based clinical

guidelines available

Screening of depression

PHQ 2

Over the past 2 weeks, how often have you been bothered by any of the following problems?

1. Little interest or pleasure in doing things.

2. Feeling down, depressed, or hopeless.

If the answer is yes to either question -- go to PHQ 9

PHQ 9Over the past 2 weeks, how often have you been bothered by any of the following problems?

1. Little interest or pleasure in doing things.

2. Feeling down, depressed, or hopeless.

3. Trouble falling asleep, staying asleep, or sleeping too much.

4. Feeling tired or having little energy.

5. Poor appetite or overeating.

6. Feeling bad about yourself, feeling that you are a failure, or feeling that you have let yourself or your family down.

PHQ 97. Trouble concentrating on things such as reading

the newspaper or watching television.

8. Moving or speaking so slowly that other people could have noticed. Or being so fidgety or restless that you have been moving around a lot more than usual.

9. Thinking that you would be better off dead or that you want to hurt yourself in some way.

Questions are scored: not at all0; several days1; more than half the days2; and nearly every day3.

< 10 Minor 10-20 moderate > 20 major

Depression Treatment in CAD• Enhancing Recovery In Coronary Heart

Disease (ENRICHD) trial is RC clinical trial evaluated 2481 patients with evidence of depression after myocardial infarction who either underwent treatment for depression (cognitive behavioural therapy) or usual care.

• Despite the treatment group's improvements in depression and social support, there was no significant difference in event-free survival (mortality and recurrent infarction) after an average follow-up of 29 months, between usual care (75.9%) and psychosocial intervention (75.8%).

Depression Treatment in CAD• Tricyclic antidepressant TCA are

contraindicated in cardiac patients due to:1. Postural hypotension

2. Arrhythmogenic effects

3. Drug interactions

• Monamine oxidase inhibitors MAOI1. Drug and food interactions

2. Second line treatment in cardiac patient

• Serotonine receptor reuptake inhibitors SSRI:

1. More safer and effective

2. Drug interaction with B-Blockers, digitalis, warfaren,

• Sertraline was found to be safe and effective in treatment of depression after AMI in SADHRT trial

• Also, citalopram proved to be safe and effective even than behavioral Treatment in CREAT study

• Paroxetine was found to be safe in cardiac patient in 2 small trials

Depression Treatment in CAD

It is reasonable to consider screening SIHD patients for depression and to refer or treat when indicated.

Treatment of depression has not been shown to improve cardiovascular disease outcomes but might be reasonable for its other clinical benefits.

I IIa IIb III

I IIa IIb III

Management of Psychological Factors

Myocardial Infarction and Depression intervention Trial MIND-IT

• The authors report that the severity of left ventricular (LV) dysfunction is significantly related to the severity of depressive symptoms during the hospitalization.

• LV dysfunction was strongly associated with BDI scores

• Use of B-Blockers was not associated with increase in depressive symptoms

• The effect of different depression treatment on CV mortality is not published yetVan Melle et. al. Eur. Heart J. 2005 and JACC

2006

Van Melle et. al. Eur. Heart J. 2005

Depression & HF

Major depression was present in 21.5% of patients with HF

Prevalence of depression increases with the increased severity of heart failure

There was a strong correlation between the presence of depression and the poor prognosis in patient with HF

Treatment of depression though did not affect the prognosis, it improves compliance to therapy and quality of life in HF patients

Rutledge et. Al. JACC 2006

Hazard of death in HF patient with depression

Milani et.al Am. J Cardiol. 2011

Post-discharge mortality in HF

Albert et. Al. Am. J Med. 2009

HF management procedures

Albert et. Al. Am. J Med. 2009

Unresolved Issues? • CAD and depression which problem lead to

the other• Treatment of depression in patient with CAD

have any implication on the prognosis of cardiovascular affection

• The best line of treatment of depression in CAD patient whether behavioral therapy or drugs or combination of both

Take home messages Depression is common disorder that affect 10-15% of the general population and associated with 20-30% of cardiac patients

This association was more in CAD, HF, HTN & arrhythmias

The mechanism of this association is multifactorial, involving endocrinal, autonomic, inflammatory, hematological & genetic factors

Although, this association increased morbidity and mortality of cardiac disease the implication of treatment of depression on cardiovascular mortality is not clear

Take home messages Routine screening of cardiac patient especially CAD for depression is very useful for management of both comorbidities

Patients with cardiac disease who are under treatment for depression should be carefully monitored for adherence to their medical care, drug efficacy, and safety with respect to their cardiovascular as well as mental health.

Coordination of care between healthcare providers is essential in patients with combined medical and mental health diagnoses.

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