Accepted Manuscript Meta-Analysis of Mental Stress-Induced Myocardial Ischemia and Subsequent Cardiac Events in Patients with Coronary Artery Disease Jingkai Wei, BMS Cherie Rooks, PhD Ronnie Ramadan, MD Amit J. Shah, MD, MSCR J. Douglas Bremner, MD Arshed A. Quyyumi, MD Michael Kutner, PhD Viola Vaccarino, MD, PhD PII:

S0002-9149(14)01036-4

DOI:

10.1016/j.amjcard.2014.04.022

Reference:

AJC 20426

To appear in:

The American Journal of Cardiology

Received Date: 2 March 2014 Revised Date:

22 April 2014

Accepted Date: 23 April 2014

Please cite this article as: Wei J, Rooks C, Ramadan R, Shah AJ, Bremner JD, Quyyumi AA, Kutner M, Vaccarino V, Meta-Analysis of Mental Stress-Induced Myocardial Ischemia and Subsequent Cardiac Events in Patients with Coronary Artery Disease, The American Journal of Cardiology (2014), doi: 10.1016/j.amjcard.2014.04.022. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Meta-Analysis of Mental Stress-Induced Myocardial Ischemia and Subsequent Cardiac Events in Patients with Coronary Artery Disease

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Running title: Mental Stress-Induced Ischemia and Cardiac Events

Jingkai Wei, BMS;a Cherie Rooks, PhD;a Ronnie Ramadan, MD;b Amit J. Shah, MD, MSCR,a,b J.

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Douglas Bremner, MD,c Arshed A Quyyumi, MD;b Michael Kutner, PhD;d

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Viola Vaccarino, MD, PhDa, b

a. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA b. Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA

Atlanta, GA

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c. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine,

d. Department of Biostatistics, Rollins School of Public Health, Emory University, Atlanta, GA

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Corresponding author:

Viola Vaccarino, MD, PhD

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Emory University, Department of Epidemiology, Rollins School of Public Health, 1518 Clifton Rd NE, Room 3011, Atlanta, GA 30322 Phone: 404-727-8710; Fax: 404-727-8737; email: [email protected]

Sources of Funding: This work was supported by R01 HL109413, 2R01 HL068630, 2K24HL077506, K24 MH076955, R01 HL088726, P01 HL 101398, KL2TR000455 and UL1TR000454 from the National Institutes of Health.

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ABSTRACT Mental stress-induced myocardial ischemia (MSIMI) has been associated with adverse prognosis

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in patients with coronary artery disease (CAD), but whether this is a uniform finding across different studies has not been described. We conducted a systematic review and meta-analysis of prospective studies examining the association between MSIMI and adverse outcome events among patients with stable CAD. We searched PubMed, Embase, Web of Science and PsycINFO

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databases for English language prospective studies of CAD patients who underwent standardized mental stress testing to determine presence of MSIMI and were followed for subsequent cardiac

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events or total mortality. Our outcomes of interest were CAD recurrence, CAD mortality, or total mortality. A summary effect estimate was derived using a fixed-effects meta-analysis model. Only five studies, each with a sample size of 5% by RNV

Non-fatal MI, revasc, or cardiac death

28

67%

7%

Krantz (1999)12

79

4%

58.0

3.5 y (2.7-7.3y)

PS/5 min; Arithmetic/5 min;

WMA by echocardiography or RNV

Non-fatal MI, revasc, or cardiac death

28

57%

18%

Sheps (2002)13

182

14%

63.0

5.2+0.4 y

PS/5 min; ST/5 min

All-cause mortality

15

20%

7%

Babyak (2010)14

138

30%

62.0

5.9 y (35 d – 8.8 y)

PS/5 min; MT/5 min

Non-fatal MI or all-cause mortality

32

19%

4%

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Stressor/Length

No. of Events

Study

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WMA by RNV

Reduction in LVEF ≥ 5% by RNV

Abbreviations: CAD: Coronary Artery Disease; ECG: Electrocardiography; LVEF: Left Ventricular Ejection Fraction; MI: Myocardial Infarction; MSIMI: Mental Stress-Induced Myocardial Ischemia; MT: Mirror Tracing; PS: Public Speaking; Revasc: revascularization procedures; RNV: Radionuclide Ventriculography; SI: Structural Interview;

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ST: Stroop Test; WMA: Wall Motion Abnormalities.

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Table 2. Quality assessment of the five studies included in the meta-analysis according to the Newcastle Ottawa Scale. Comparability

Exposed Cohort Representative

Selection of Non- Exposed Cohort

Ascertainment of Exposure

Outcome not Present at Baseline

Jain (1995)10

0

1

1

1

Jiang (1996)11

0

1

1

Krantz (1999)12

0

1

1

Sheps (2002)13

0

1

Babyak (2010)14

0

1

Mean Score

0

1

Analysis Adjusted for Confounding Factors

Total Score

Length of Follow-up

Adequacy of Follow-up

0.5

1

1

0

5.5

1

1

1

1

1

7

1

0.5

1

1

1

6.5

1

1

0.5

1

1

1

6.5

1

1

1

1

1

1

7

1

0.7

1

1

0.8

6.5

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1

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Assessment of Outcome

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Study

Outcome

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Selection

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Appendix: Terms Used in the Literature Search

Pubmed (1) "Myocardial Ischemia"[Mesh]

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(2) “stress, psychological”[Mesh] (3) (1) AND (2) Embase

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(1) 'mental stress'/exp (2) 'ischemic heart disease'/exp

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(3) (1) AND (2)

Web of Science (1) mental* stress* (2) psychologic* stress* (3) ischemi*

PsycInfo (1) mental stress

(3) Ischemia

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(2) psychological stress

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(4) ((1) OR (2)) AND (3)

(4) ischemic heart disease

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(5) ((1) OR (2)) AND ((3) OR (4))