Overview 

Coronary heart disease (CHD) is a common

disease and cause of death in women,

accounting for over 250,000 deaths in women

per year. Over the last two decades, multiple

important studies have helped define accurate

clinical tests, risk factors, preventive

interventions, and effective therapies for CHD.

Unfortunately, many of these studies have either

excluded women entirely or included only

limited numbers of women and minorities.

Thus, much of the evidence supporting

contemporary recommendations for testing,

prevention, and treatment of coronary disease in

women is extrapolated from studies conducted

predominantly in middle-aged men. The two

best approaches to obtain additional evidence on

diagnosis and treatment of CHD in women are

to conduct large studies that include adequate

numbers of women and minorities to answer the

research question or to perform systematic

reviews and meta-analyses summarizing effect

estimates by subgroup.

The Agency for Healthcare Research and

Quality (AHRQ) and the National Institutes of

Health Office of Research on Women's Health

funded the University of California, San

Francisco (UCSF)-Stanford Evidence-based

Practice Center (EPC) to review the evidence

regarding prevention, diagnosis, and

management of coronary heart disease in

women and minorities. In an initial phase of

this work, the UCSF-Stanford EPC conducted a

preliminary review of evidence on 42 topics

related to CHD in women, titled Results of

Systematic Review of Research on Diagnosis and

Treatment of Coronary Heart Disease in Women.1

Based on these reviews, we identified four key

questions for systematic review and metaanalysis. The results of these four reviews are

presented in this report.

Key Questions

1. What is the accuracy of noninvasive tests

for diagnosis of CHD in women: exercise

myocardial perfusion imaging (MPI) and

exercise echocardiography?

a. What are the summary estimates of

sensitivity, specificity and likelihood

ratios for exercise MPI and exercise

echocardiography in women?

b. What is the accuracy of exercise MPI

and exercise echocardiography in

women compared to men?

2. What is the effectiveness of treatment with

lipid lowering drugs for reducing CHD risk

in women with and without CHD?

a. What is the effectiveness of drug

treatment in reducing total mortality,

CHD mortality, CHD events or CHD

procedures in women with known

CHD and those without known CHD?

3. What is the relative risk for CHD in

women with type 2 diabetes?

a. What is the relative risk for CHD in

women with type 2 diabetes compared

to women without diabetes?

Evidence Report/Technology Assessment

Number 81

Diagnosis and Treatment of Coronary Heart

Disease in Women: Systematic Reviews of

Evidence on Selected Topics

Summary

Agency for Healthcare Research and Quality

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service

1 Grady D, Chaput L, Kristof M. Results of Systematic Review of Research on Diagnosis and Treatment of Coronary Heart

Disease in Women. Evidence Report/Technology Assessment No. 80. (Prepared by the University of California, San

Francisco-Stanford Evidence-based Practice Center under Contract No 290-97-0013.) AHRQ Publication No. 03-0035.

Rockville, MD: Agency for Healthcare Research and Quality. May 2003.
b. Does the relative risk for CHD differ between women

and men with type 2 diabetes?

4. What is the prognostic value of troponin for CHD in

women?

a. What is the impact of troponin on risk for death

among women with non-ST elevation acute coronary

syndromes?

b. Does the prognostic value of troponin for mortality

differ between men and women?

c. What is the impact of troponin on risk for death or

myocardial infarction for women with non-ST

elevation acute coronary syndromes?

d. Does the prognostic value of troponin for mortality

or myocardial infarction differ between men and

women?

For each of the four questions, we also attempted to

identify and summarize evidence stratified by race or ethnicity. 

Methodology

We performed standardized searches of electronic databases

of publications relevant to the topic areas. We developed

specific search terms for each of the four key topics and

conducted a separate search for evidence regarding each. We

also reviewed the bibliographies of retrieved articles and

sought suggestions for additional articles from our expert peer

reviewers. For each topic area, we established clear inclusion

criteria that required that studies provide data regarding the

research question specific to women. 

For three of the key questions (noninvasive diagnostic tests,

lipid lowering and diabetes), two UCSF-Stanford EPC

investigators reviewed all identified titles and excluded those

that did not meet inclusion criteria. The abstracts of remaining

articles were reviewed by two UCSF-Stanford EPC physician

investigators, who independently classified eligibility. The full

text of the remaining eligible articles was reviewed

independently by two UCSF-Stanford EPC physician

investigators using standardized abstraction forms to classify

eligibility, rate quality as fair or good based on predefined

criteria, and abstract data for eligible studies. For the key

question regarding troponin, titles and abstracts were reviewed

by one UCSF-Stanford EPC investigator. Data were

abstracted from each eligible article by two independent

reviewers and entered on standardized electronic data forms. 

Accuracy of exercise myocardial perfusion

imaging and echocardiography for diagnosis

of CHD in women

We searched PubMed®, the Cochrane Database, and

DARE for articles in English and other languages published

from 1990 through January 2002. We used the following

search terms to identify cross-sectional studies in which the

accuracy of the exercise MPI or exercise echocardiography was

compared to angiographic findings:

(Note: An asterisk indicates truncation of the search term.)

• Exercise MPI: thallium radioisotopes,

radiopharmaceuticals, tomography emission-computed

single-photon, technetium TC 99M sestamibi,

organotechnetium compounds, Spect, Cardiolite, Mibi

AND exercise, exercise test, exercise tolerance, exercise*,

exercising, "stress test" AND diagnosis, diagnoses,

diagnostic, diagnosing, predictive values of test

• Exercise echocardiography: echocardio*, ultrasound,

ultrasonography

AND exercise, exercise test, exercise tolerance, exercise*,

exercising, "stress test"

AND diagnosis, diagnoses, diagnostic, diagnosing,

predictive values of test

• Outcomes: cardiovascular diseases, heart diseases,

myocardial ischemia, coronary disease

Searches for noninvasive diagnostic tests identified 3,136

titles. After eliminating ineligible studies by review of titles

and abstracts, we reviewed the full text of 326 articles and

found 14 eligible cross-sectional studies with data on women

that were included in the systematic review. Ten studies

examined the accuracy of MPI and four examined the

accuracy of exercise echocardiography. 

Efficacy of lipid lowering to reduce risk of

CHD in women

We searched PubMed®, the Cochrane Database, and

DARE for articles in English and other languages published

from 1966 through January 2002. We used the following

search terms to identify clinical trials: 

• Lipid lowering: hyperlipidemia and anticholesteremic

agents, antilipemic agents, simvastatin, lovastatin,

pravastatin, atorvastatin, fluvastatin, gemfibrozil,

cholestyramine, cholestpol, niacin

• Outcomes: cardiovascular diseases, heart diseases,

myocardial ischemia, coronary disease

Searches for clinical trials of lipid lowering treatment

identified 1,335 titles. After eliminating ineligible studies by

review of titles and abstracts, we reviewed the full text of 120

articles and found 11 eligible randomized trials that provided

data on women and were included in the systematic review.

Diabetes as a risk factor for CHD in women

We searched PubMed®, the Cochrane Database, and

DARE for articles in English and other languages published

from 1966 through January 2002. We used the following

search terms to identify cohort and cross-sectional studies:

2
• Diabetes: diabetes

• Outcomes: cardiovascular disease, myocardial infarction,

ischemic heart disease

Searches for diabetes as a risk factor for CHD in women

identified 4,578 titles. After eliminating ineligible studies by

review of titles and abstracts, we reviewed the full text of 233

articles. We found 17 studies that fulfilled all inclusion

criteria; 12 were prospective cohort studies and five were crosssectional analyses.

Prognostic value of troponin for CHD in

women

We searched MEDLINE® for articles in English and other

languages published from 1966 through January 2002. We

used the following search terms to identify clinical trials or

cohort studies:

• The text word troponin, and

• The text words angina or unstable or myocardial infarction

or ischemia. 

We also performed a search of EMBASE from 1990-1998,

but did not find any additional articles fulfilling the study

criteria. 

Searches identified 1,049 articles. We excluded 878 articles

based on title or abstracts and reviewed the full text of 171

articles. Of these, eight eligible studies provided data on

women and were included in the systematic review; six were

clinical trials and two were cohort studies. 

Findings 

Overall

• Data from many otherwise eligible studies could not be

included in the systematic reviews because the findings

were not stratified by sex. We identified 82 studies that

included women, but did not stratify the data by sex. We

contacted authors of these studies twice requesting data on

women but received data from only 19 studies (23

percent). 

• Little evidence was available regarding the key questions as

they pertain to women of different races/ethnicities. For

this reason, only the review of diabetes as a risk factor for

CHD provides summary findings by ethnicity. 

Accuracy of exercise myocardial perfusion

imaging and echocardiography for diagnosis

of CHD in women

• Although 34 eligible studies of the accuracy of exercise

myocardial perfusion imaging or exercise echocardiography

included women, only nine published results by sex. By

contacting study investigators, we were successful in

obtaining data on women from five additional studies.

Thus, we were able to analyze results from 14 studies that

included 893 women. Ten studies examined the accuracy

of myocardial perfusion imaging and four examined the

accuracy of exercise echocardiography.

• In women, the overall accuracy of both exercise myocardial

perfusion imaging and exercise echocardiography for

diagnosis of CHD is low with positive likelihood ratios of

2.5 to 3 and negative likelihood ratios of about 0.3.

• The accuracy of exercise myocardial perfusion imaging for

diagnosis of CHD is not clinically different in women

compared to men.

• There is little difference in the accuracy of exercise

myocardial perfusion imaging and exercise

echocardiography for diagnosis of CHD in women.

• The accuracy of exercise myocardial perfusion imaging for

diagnosis of CHD is similar whether thallium or sestamibi

is used as the imaging agent. 

Efficacy of lipid lowering to reduce risk of

CHD in women 

• Although 20 clinical trials of the effects of lipid lowering

therapy included women, only nine published results by

sex. By contacting study investigators, we were successful in

obtaining data on women from two additional trials. Thus,

we were able to analyze results from 11 trials that included

15,917 women. 

• In women with known CHD, treatment with lipid

lowering therapy reduces risk of CHD mortality 26

percent, nonfatal myocardial infarction (MI) 36 percent

and major CHD events 21 percent. There was insufficient

evidence to show that lipid lowering reduces rates of

revascularization procedures and no evidence of a

reduction of risk in total mortality.

• For women without CHD, there is insufficient evidence to

determine whether lipid lowering reduces risk for any

clinical outcome. 

Diabetes as a risk factor for CHD in women

• Although 36 eligible studies included women, only 10

published results by sex. By contacting study investigators,

we were successful in obtaining data on women from seven

additional studies. Thus, we were able to analyze results

from 17 studies that included 43,944 women (4,522 with

diabetes and 39,422 without diabetes). 

• Adjusted summary odds ratios (ORs) for CHD mortality

and nonfatal MI due to diabetes are higher among women

than men, but summary ORs for all-cause mortality are

slightly higher in men than women. All of the differences

are modest and not statistically significant. 

• The summary OR for CHD mortality due to diabetes is

2.9 (95% confidence interval [CI], 2.2-3.8) for women

and 2.3 (95% CI, 1.9-2.8) for men. The summary OR for

nonfatal MI due to diabetes is 1.7 (95% CI, 1.3-2.3) for

women and 1.6 (95% CI, 1.1-2.2) for men. The summary

3
OR for all-cause mortality due to diabetes is 1.9 (95% CI,

1.7-2.3) for women and 2.1 (95% CI, 1.7-2.7) for men.

• Summary estimates for risk of CHD mortality due to

diabetes for white men and women are similar to those for

all ethnicities combined.

• The difference in relative risk for CHD outcomes between

men and women is progressively attenuated with

adjustment for major cardiovascular risk factors. This

finding may be due to the fact that women with diabetes

have more risk factors or more severe risk factor

abnormalities in comparison to women without diabetes

than is the case for men with and without diabetes.

Prognostic value of troponin for CHD in

women

• We reviewed the full text of 171 articles and found three

eligible studies with data on women. Nine additional large

studies of the prognostic value of troponin included

women, but did not provide data stratified by sex. After

contacting authors, we obtained data for women from five

of these studies. Thus, we identified eight eligible studies

that provided data on 3,169 women and 4,070 men. 

• Elevated troponin was observed in 35 percent of women

and 39 percent of men with non-ST elevation acute

coronary syndromes.

• Women with acute coronary syndromes were older and

more likely to have diabetes and hypertension than men

with acute coronary syndromes.

• Elevated troponin indicates a similar increase in risk of

death for both women (summary OR 2.63; 95% CI, 1.75-

3.95) and men (summary OR 2.83; 95% CI, 1.92-4.17).

• Elevated troponin indicates a greater increase in risk of

nonfatal MI for women (summary OR 1.80; 95% CI,

1.28-2.54) than men (summary OR 1.06; 95% CI, 0.8-

1.41).

Future Research 

The major problem in performing these systematic reviews

was lack of availability of data on women and minority

populations. Many studies that include women did not

provide estimates stratified by sex. Attempts to obtain

unpublished data from women were time-consuming and only

modestly successful.

Recommendations for future research follow.

Overall

• Future studies that include women should publish or make

available outcomes stratified by sex and ethnicity. 

Accuracy of exercise myocardial perfusion

imaging and echocardiography for diagnosis

of CHD in women

• The quality of future studies of the accuracy of noninvasive

tests for the diagnosis of CHD should be improved by

excluding persons with known CHD, performing both the

noninvasive test and angiography in all participants and

assuring that the outcome of the noninvasive test is assessed

by personnel blinded to the results of angiography.

• Future research should address ways to improve accuracy of

noninvasive tests for CHD in both men and women.

Efficacy of lipid lowering to reduce risk of

CHD in women

• Future clinical trials should include adequate numbers of

women to determine the effect of lipid lowering in women

at high risk but without known CHD.

Diabetes as a risk factor for CHD in women

• Future prospective studies should present sex- and

race/ethnicity-specific fatal and nonfatal coronary disease

endpoints before and after adjustment for established

CHD risk factors. 

• Future studies should attempt to clarify the effect of

established risk factors, which cluster in women with

diabetes, compared to the effect of diabetes itself in

increasing risk for CHD among women with diabetes.

Prognostic value of troponin for CHD in

women

• Future studies are needed to verify and explore why the

prognostic value of elevated troponin results for nonfatal

MI is different in women compared to men. 

Availability of the Full Report

The full evidence report from which this summary was

taken was prepared for the Agency for Healthcare Research

and Quality (AHRQ) by the University of California, San

Francisco-Stanford Evidence-based Practice Center, under

Contract No. 290-97-0013. It is expected to be available in

May 2003. At that time, printed copies may be obtained free

of charge from the AHRQ Publications Clearinghouse by

calling 800-358-9295. Requesters should ask for Evidence

Report/Technology Assessment No. 81, Diagnosis and

Treatment of Coronary Heart Disease in Women: Systematic

Reviews of Evidence on Selected Topics. In addition, Internet

users will be able to access the report and this summary online

through AHRQ’s Web site at www.ahrq.gov.

AHRQ Pub. No. 03-E036

May 2003

ISSN 1530-440X