Why is exercise treadmill testing less sensitive for detecting coronary artery disease in women compared to men?

Why Exercise Testing Has Lower Sensitivity for CAD Detection in Women

Exercise treadmill testing has reduced sensitivity in women primarily because women achieve lower functional capacity and frequently fail to reach adequate heart rate targets during exercise, resulting in submaximal stress that prevents provocation of myocardial ischemia before premature peripheral fatigue terminates the test. 1

Primary Physiological Mechanisms

Reduced Exercise Capacity

• Women have significantly lower work capacity on exercise tests, averaging only 5-7 minutes of exercise duration, which challenges the ability to provoke myocardial ischemia due to premature peripheral fatigue. 1
• Women engage less often in physical exercise programs, have lower baseline functional capacity, and experience more functional decline during their menopausal years compared to men. 1
• This submaximal stress directly impairs sensitivity because inadequate cardiac stress fails to unmask flow-limiting coronary stenoses. 1

Inadequate Heart Rate Response

• Women referred for stress testing are often older (due to delayed onset of CAD compared to men) and are less likely to reach adequate target heart rates during exercise testing. 1
• Failure to achieve ≥85% of age-predicted maximum heart rate without symptoms or ECG changes renders the test inconclusive rather than truly negative. 1
• The influence of submaximal stress on sensitivity is a recognized sex-specific limitation that reduces the test's ability to detect obstructive disease. 1

Quantitative Diagnostic Performance

Meta-Analysis Data

• In a meta-analysis of 19 exercise ECG studies including 3,721 women, sensitivity was only 61% compared to 72% in 1,977 men. 1
• Even with modified exercise protocols specifically designed for women, sensitivity remained poor at 31-43% in women with angiographically confirmed CAD. 2
• Among Chinese women, pooled sensitivity was 80% but this varied significantly by menopausal status, with premenopausal/perimenopausal women showing particularly poor performance. 3

Clinical Context

• In the WISE study of 96 women undergoing clinically indicated coronary angiography, only 9 of 29 women (31%) with ≥50% stenosis had abnormal exercise tests, demonstrating the profound sensitivity limitation. 2
• The false-negative rate in women was considerably lower than men (17% vs 32%), but this reflects the overall lower sensitivity rather than superior performance. 4

Additional Contributing Factors

Baseline ECG Abnormalities

• Women more frequently have resting ST-T wave changes, lower ECG voltage, and hormonal factors (endogenous estrogen in premenopausal women, hormone replacement therapy in postmenopausal women) that interfere with accurate ST-segment interpretation. 1
• These baseline abnormalities reduce both sensitivity and specificity, though the impact on sensitivity is particularly problematic when combined with submaximal exercise. 1

Age and Disease Prevalence

• Because CAD onset is delayed in women compared to men, women referred for testing tend to be older with more comorbidities that limit exercise capacity. 1
• Older women are more likely to have orthopedic limitations, deconditioning, or other factors that prevent adequate exercise stress. 5

Clinical Implications and Recommendations

When to Bypass Standard Exercise ECG

• Women expected to perform <5 METs based on the Duke Activity Status Index (DASI) should be evaluated with pharmacological stress imaging rather than standard exercise ECG. 1
• Women who cannot achieve adequate exercise due to deconditioning, obesity, peripheral artery disease, COPD, or orthopedic limitations should proceed directly to pharmacological stress testing. 5

Alternative Testing Strategies

• Stress echocardiography provides significantly higher specificity and accuracy than standard exercise ECG testing in women, with sensitivity ranging from 71-97%. 1, 6
• Despite the lower sensitivity of exercise ECG, it maintains high negative predictive value in women with low pretest probability of CAD and low-risk Duke treadmill scores. 1
• Integration of multiple parameters (Duke treadmill score, heart rate recovery, functional capacity) improves diagnostic accuracy beyond ST-segment analysis alone. 1, 7

Important Caveat

• Women who develop inducible ischemia at low workloads (<5 METs) have a high likelihood of obstructive coronary disease and should be referred directly to coronary angiography rather than repeat testing. 1
• The prognostic value of exercise testing variables (particularly chronotropic incompetence) may actually be stronger in women than men for predicting myocardial infarction, despite lower diagnostic sensitivity. 8