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The WISE Study: The NHLBISponsored Womens Ischemia Syndrome Evaluation Methods and Findings

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Women and Heart Disease - 3. Prevalence of Obstructive CAD at Angiography in Women ... International Symposium on Women's Health and Menopause ... – PowerPoint PPT presentation

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Title: The WISE Study: The NHLBISponsored Womens Ischemia Syndrome Evaluation Methods and Findings


1
The WISE StudyThe NHLBI-Sponsored Womens
Ischemia Syndrome EvaluationMethods and Findings
  • B. Delia Johnson, Ph.D.
  • Research Associate, EDC
  • Epidemiology Seminar Series, October 6, 2005
  • Graduate School of Public Health, University of
    Pittsburgh

2
Outline
  • Background
  • WISE Overview
  • Key Findings
  • Implications / Impact

3
Background
4
Women and Heart Disease - 1
5
Women and Heart Disease - 2
Cardiovascular Disease Mortality Trends for Males
and Females United States 1979-2002
6
Women and Heart Disease - 3
  • Prevalence of Obstructive CAD at Angiography in
    Women

7
What is Myocardial Ischemia?
  • Insufficient amount of oxygen reaching the heart
    muscle
  • Often exercise or anxiety induced
  • Reversible dysfunction or prolonged severe
  • Chest pain or silent
  • Transient ECG abnormalities
  • Over time, the affected heart tissue may die
  • Many possible causes
  • Obstructed coronary arteries (CAD)
  • Endothelial dysfunction
  • coronary vasoconstriction
  • Microvascular insufficiency.

8
WISE Overview
The Womens Ischemia Syndrome Evaluation
9
WISE Goals
  • 1. Develop accurate diagnostic approaches for CAD
    detection in women.
  • 2. Determine the frequency, pathophysiology, and
    significance of myocardial ischemia in the
    absence of significant CAD in women.
  • 3. Evaluate the influence of hormones on
    pathophysiology and diagnostic test response.

10
In Brief
  • A four-center NHLBI-sponsored study
  • 936 women undergoing clinically ordered coronary
    angiography
  • Observational study

11
Observational Study
  • A type of study in which individuals are observed
    or certain outcomes measured
  • No attempt to affect the outcome (e.g. no
    treatment)
  • Advantage natural setting
  • Drawbacks - Hawthorne effect
  • - Association vs. causality
  • Low in Hierarchy of Evidence - ???
  • Concato 2004, NeuroRx 1341-7.

12
Data Collection - 1
  • All Sites WISE Core Data
  • Core lab quantitative angiographic analysis
  • Demographics (age, race)
  • CAD risk factors (smoking, diabetes)
  • Medical hx (comorbidities, meds)
  • Reproductive hx (hysterectomy, HRT use)
  • Physical exam (weight, BP)
  • DASI (functional capacity)
  • Symptom history
  • Psychological inventories (Beck, Spielberger)
  • Block dietary data
  • Baseline ECG
  • Annual follow-up (adverse events, resource use)
  • Study termination (lost to FU, withdrew consent).

13
Data Collection - 2
  • All Sites Core Lab Blood Assays
  • Lipids (HDL, triglycerides)
  • Reproductive hormones (estradiol, FSH)
  • Androgens (testosterone, androsteindione)
  • Inflammatory markers (hs-CRP, SAA)
  • Phytoestrogens (genistein, daidzein)
  • Insulin, fasting glucose.

14
Data Collection - 3
  • 3. Site-Specific Diagnostic Tests ( done)
  • Provocative coronary reactivity (coronary
    diameter change, flow reserve) (166)
  • Brachial artery ultrasound (381)
  • Exercise ECG (289)
  • Pharmacological ECG (289)
  • Dobutamine stress echo (171)
  • SPECT (radionuclide perfusion) (452)
  • MRI perfusion (177)
  • LV mass (107)
  • Holter monitoring (163)
  • P-31 (MRI spectroscopy) (292)
  • PROCEDURAL SYMPTOM QUESTIONNAIRE

15
WISE Organization
NHLBI
DSMB
Steering Committee
Coordinating Center
Core Laboratories Angiographic Hormones,
androgens, insulin, glucose Coronary
reactivity Brachial Artery ECG Lipids Phytoestroge
ns Inflammatory markers P31
PP Committee
Subcommittees Symptoms Psychosocial Hormones Mor
tality classification P31 Ischemia
Clinical Centers Univ. Alabama Medical Center
Birmingham Univ. Florida, Gainesville UPMC,
Pittsburgh Allegheny General Hosp. Pittsburgh
16
WISE Timeline - 1
Sept. 1996
Oct. 2005
2000
8557 women screened 22 eligible 50 of these
enrolled (N936)
WISE Extension Annual Follow-Ups
  • WISE Extension Goals
  • Determine incremental prognostic value of novel
    WISE tests
  • Determine prognostic value of female
    reproductive variables
  • Determine cost effectiveness of WISE tests
  • Genetics
  • Inflammatory markers

17
WISE Timeline - 2
Sept. 1996
Oct. 2005
2000
8557 women screened 22 eligible 50 of these
enrolled (N936)
WISE Extension Annual Follow-Ups
ARIC
FemHRT
IVUS
WTH
EWISE
QWISE
YWISE
Sildenafil
WISE Ancillary Studies
18
Population Characteristics - 1
19
Population Characteristics - 2
20
Reasons for Catheterization
21
Key Findings
22
WISE Goals
  • Develop accurate diagnostic approaches for CAD
    detection in women.
  • Is classic angina diagnostic for CAD in women?
  • 2. Determine the frequency, pathophysiology, and
    significance of myocardial ischemia in the
    absence of significant CAD in women.
  • 3. Evaluate the influence of hormones on
    pathophysiology and diagnostic test response.

23
Chest Pain / Angina
  • 481 WISE women
  • Symptomatic in prior year
  • No prior MI or procedure
  • 26 with CAD

24
Angina Determination
  • Ask are your symptoms
  • Substernal
  • Exertional / strong emotion
  • Relieved w/in 10 minutes by rest/nitroglycerin
  • Definitions of Angina
  • Typical Angina all 3 present
  • Atypical Angina 2 out of 3 present
  • Nonanginal chest pain 1 present
  • Asymptomatic 0 present

25
Probability CAD by Anginal Classification and
Age in Women
Age 35-45
Age 45-55
Age 55-65
Age 65-75
Data from Diamond (1980 J Clin Invest.
651210-21)
26
Probability vs. WISE Prevalence of CAD by
Anginal Classification and Age
Age 45-55, n141
Age 35-45, n57
Age 65-75, n114
Age 55-65, n137
Adjusted for diabetes, dyslipidemia, smoking,
SBP Source Johnson et al. Chapter 10 in Shaw
Redberg (Eds.) Contemporary Cardiology Coronary
Disease in Women. Humana Press 2004.
27
Angina - Conclusions
  • Overall, typical angina is not a good diagnostic
    indicator of CAD in women
  • After age 55, classic angina classification is
    moderately predictive of CAD.

28
WISE Goals
  • Develop accurate diagnostic approaches for CAD
    detection in women.
  • 2. Determine the frequency, pathophysiology, and
    significance of myocardial ischemia in the
    absence of significant CAD in women.
  • Is metabolic dysfunction in the heart predictive
    of cardiovascular outcomes?
  • 3. Evaluate the influence of hormones on
    pathophysiology and diagnostic test response.

29
P-31 Spectroscopy Metabolic Dysfunction
  • Spectra from Woman Volunteer
  • LV chamber
  • Interventricular septum
  • LV anterior wall
  • Phosphorus-31 nuclear magnetic resonance
    spectroscopy (MRS)
  • Normal PCr/ATP ratio 1.6
  • 74 WISE women w/o CAD.
  • PCr/ATP ratio measured before after handgrip
    stress
  • Abnormal defined
  • Measure of metabolic function in heart muscle

30
P-31 Normal vs. Abnormal
No consistent relationship of CAD risk factors in
normal vs abnormal MRS
31
P-31 Spectroscopy Outcomes
Risk adjusted p0.02
Source Johnson, Circulation 2004
32
P-31 Spectroscopy - Conclusion
  • Abnormal MRS spectroscopy results are found in
    about 20 of women with chest pain but no CAD
  • This abnormality is predictive of cardiovascular
    events ischemia-related hospitalization.

33
WISE Goals
  • 1. Develop accurate diagnostic approaches for CAD
    detection in women.
  • 2. Determine the frequency, pathophysiology, and
    significance of myocardial ischemia in the
    absence of significant CAD in women.
  • 3. Evaluate the influence of hormones on
    pathophysiology and diagnostic test response.
  • Is there a relationship between endogenous
    reproductive hormones and CAD?

34
Hypothalamic Hypoestrogenemia
  • 95 premenopausal WISE women
  • No exogenous hormones (OC)
  • HypoE defined as E2LH
  • 13 (14) had CAD
  • 33 (35) had hypoE
  • 26 non-white (mostly AA)

35
HypoE CAD
p0.01
36
HypoE CADReproductive Hormones
37
HypoE CADMultivariate Models
Independent Predictors of CAD
Independent Predictors of HypoE
c 0.86
NS variables age, race, HTN, diabetes, BMI, WHR,
smoking, family Hx, lipids, Beck depression,
stress, typical angina.
c 0.70
38
Hypoestrogenemia - Conclusions
  • Premenopausal women with obstructive CAD are
    highly likely to have hypothalamic
    hypoestrogenemia
  • This condition is related to anxiety (as
    suggested by anti-anxiety medications) and
    diabetes.

39
Summary of Key Findings
  • Diagnostic approaches for CAD Detection
  • Chest pain is not a good indicator of CAD in
    women
  • Myocardial Ischemia
  • Coronary metabolic dysfunction occurs in about
    20 of women with chest pain and no CAD
  • It is highly predictive of CV events in these
    women
  • Influence of Hormones
  • Angiographic PRE women with CAD are highly likely
    to have hypothalamic hypoestrogenemia.

40
Publications / Publicity - 1
  • 57 peer-reviewed publications. Additional
    topics
  • Markers of ischemia
  • Psychosocial / socioeconomic / ethnicity
  • Obesity / metabolic syndrome
  • Functional capacity
  • Inflammatory markers / biomarkers
  • Genetics
  • Quality of care
  • Cost assessment
  • Renal insufficiency / anemia / diabetes
  • WISE menopausal algorithm
  • Novel risk factors

41
Publications / Publicity - 2
  • WISE workshops
  • AHA Scientific Conference on Molecular,
    Integrative and Clinical Approaches to Myocardial
    Ischemia, August 2001.
  • Womens Ischemic Syndrome Evaluation. Current
    Status Future Research Directions (NIH/NHLBI),
    October 2-4, 2002.

42
Publications / Publicity - 3
  • 118 abstracts at scientific meetings
  • American Heart Association
  • American College of Cardiology
  • Society for Cardiovascular Magnetic Resonance
  • International Congress on Coronary Artery Disease
  • North American Menopause Society
  • Inter-American Society of Hypertension
  • American Psychosomatic Society
  • AHA Forum on Quality of Care and Outcomes
    Research in Cardiovascular Disease and Stroke
  • European Society of Cardiology
  • International Society for Magnetic Resonance in
    Medicine
  • Society for Cardiac Angiography and Interventions
  • AHA Council on Cardiovascular Disease
    Epidemiology
  • International Symposium on Womens Health and
    Menopause
  • American Society for Clinical Pharmacology and
    Therapeutics
  • Heart Failure Society of America
  • First International Conference on Women, Heart
    Disease and Stroke
  • World Congress of Cardiology

43
Publications / Publicity - 4
44
Impact
45
Future Plans
  • WISE 3
  • A new cohort
  • Apply new knowledge
  • Learn from past mistakes
  • Validate our findings
  • generate new hypotheses
  • Clinical Trials

46
WISE Women and Men
  • Sherry Kelsey, PhD
  • Kevin Kip, PhD
  • Richard Holubkov, PhD
  • Marian Olson, MS
  • Genevieve Barrow, MS
  • Candace McClure, BS
  • Gretchen Gierach, MPH
  • Angela Pattison, BS
  • Joe Bondi, BA

47
Back-Up Slides
48
WISE Exclusion Criteria
  • Comorbidity compromising 1-year follow-up
  • Pregnancy
  • Contra-indications to provocative diagnostic
    testing
  • Cardiomyopathy
  • NY Heart Association functional Class III-IV
    congestive heart failure
  • Recent MI
  • Significant valvular / congenital heart disease
  • Language barrier to questionnaire testing.
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