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Is there a gender difference in noninvasive coronary imaging? Multislice computed tomography for noninvasive detection of coronary stenoses
© Dewey et al; licensee BioMed Central Ltd. 2008
Received: 16 November 2007
Accepted: 29 January 2008
Published: 29 January 2008
Multislice computed tomography (MSCT) coronary angiography is the foremost alternative to invasive coronary angiography.
We sought to compare the diagnostic accuracy of MSCT in female and male patients with suspected coronary disease. Altogether 50 women and 95 men underwent MSCT with 0.5 mm detector collimation. Coronary artery stenoses of at least 50% on conventional coronary angiography were considered significant.
The coronary vessel diameters of all four main coronary artery branches were significantly larger in men than in women. The diagnostic accuracy of MSCT in identifying patients with coronary artery disease was significantly lower for women (72%) compared with men (89%, p < 0.05). Also sensitivity (70% vs. 95%), positive predictive value (64% vs. 93%), and the rate of nondiagnostic examinations (14% vs. 4%, all: p < 0.05) were significantly worse for women. The effective radiation dose of MSCT coronary angiography was significantly higher in the examination of women (13.7 ± 1.2 mSv) than of men (11.7 ± 0.9 mSv, p < 0.001), mainly as a result of the fact that the radiosensitive female breast (contributing 24.5% of the dose in women) is in the x-ray path.
Noninvasive coronary angiography with MSCT might be less accurate and sensitive for women than men. Also, women are exposed to a significantly higher effective radiation dose than men.
Since conventional coronary angiography exposes the patients not only to rare (1.7%) but relevant risks like bleeding, stroke, infarction, and dissections but also has a considerable mortality of 0.11%  a noninvasive alternative would be an important advance. At present the foremost alternative to conventional coronary angiography is multislice computed tomography (MSCT) [2–7] which has a high spatial (0.5 to 0.75 mm slice thickness) and temporal resolution (140 to 200 ms acquisition window). To reliably exclude the presence of coronary artery stenoses is the primary aim of noninvasive coronary angiography using MSCT . However, MSCT exposes the patient to radiation and requires intravenous injection of a contrast medium. For these reasons and since gender differences play a prominent role in cardiac imaging  and therapy  it appears worthwhile to examine gender differences of MSCT in detail before routine application of this technology. Thus, we prospectively analyzed the diagnostic accuracy of MSCT in women and men as part of an investigator-initiated study on noninvasive coronary angiography .
Women (n = 50)
Men (n = 95)
63.9 ± 8.6
62.6 ± 9.6
Body mass index*
26.6 ± 4.3
27.3 ± 3.4
Results of conventional coronary angiography
Scanning was performed on an MSCT scanner using 16 × 0.5 mm detector collimation (Aquilion 16, Toshiba Medical Systems, Otawara, Japan) as recently described  with retrospective ECG gating, multisegment reconstruction [7, 13], 0.4 s rotation time, 120 kV, 300 mA, and 0.2 pitch, and an average image reconstruction interval of 146 ms, which was not significantly different between women (149 ± 36 ms) and men (146 ± 37 ms). Nitrate was administered prior to MSCT to increase the coronary artery diameters and to facilitate image assessment . No beta blockers were given since the main purpose of the investigator-initiated study was to compare MSCT and magnetic resonance coronary imaging and beta blockers might have favored CT over magnetic resonance. However, 74 of the 145 patients were on chronic oral beta blocker medication (24 women, 50 men). The manual sure-start feature of the scanner was used to visualize the influx of the intravenous contrast medium (bolus-tracking) and to start image acquisition. The average breathhold time and helical scan length for covering the coronary arteries (from the left atrium to the base of the heart) were both significantly (p < 0.01) shorter for women (28.0 ± 3.0 s and 9.5 ± 1.2 cm) than men (29.6 ± 2.5 s and 10.2 ± 1.0 cm) possibly as a result of a smaller heart size in women.
Conventional coronary angiography
Conventional angiography was performed using standard techniques (Integris 3000, Philips Medical Systems, Best, the Netherlands) with the transfemoral approach after intracoronary administration of 0.1 to 0.15 mg nitroglycerin within 14 days after MSCT. Quantitative coronary angiography was done by using two orthogonal projections to identify significant diameter reductions (at least 50%) in all 15 coronary artery segments . The diameter of the reference vessel on conventional coronary angiography had to measure at least 1.5 mm for a stenosis to be included in the analysis of diagnostic accuracy of MSCT, thus covering all stenoses that are possible targets for revascularization. If a coronary artery contained more than one significant stenosis, the most proximal one determined the diagnostic accuracy for the assessment of that coronary artery, since restricted flow resulting from a proximal stenosis can limit assessment of distal stenoses on noninvasive imaging .
Data and image analysis
The results of conventional coronary angiography served as the reference standard for assessing the per-patient sensitivity, specificity, accuracy, nondiagnostic rate, and negative and positive predictive values of CT for detection of significant coronary stenoses (at least 50% diameter reduction, as described above) in each patient in an intention-to-diagnose design (all patients were included regardless of image quality) . Nondiagnostic patients were defined as patients with no stenosis seen on MSCT and at least one main coronary branch with nondiagnostic image quality (relevant motion artifacts or decreased contrast precluding evaluation for the presence of stenoses in at least one segment in this main coronary branch). CT image analysis was performed using an automatic vessel detection tool with curved multiplanar reformations along the vessels and orthogonal cross-sections .
Effective radiation exposure during MSCT was estimated for all patients on the basis of individual helical scan lengths using CT-Expo 1.3 . Using the same software, relative organ doses contributing to the effective dose were estimated for women and men with a scan range of 10 cm and the CT scanning parameters described above. Image noise, contrast-to-noise ratios, the coronary vessel lengths, and the relative vessel lengths free of motion artifacts (vessel contour uninterrupted and clearly delineated) were estimated on curved multiplanar reformations of MSCT as recently described in detail elsewhere [7, 18]. Briefly, image noise was measured as the SD of density in a 10-mm2 region-of-interest in the ascending aorta and contrast was calculated by dividing densities in 5-mm2 regions-of-interest in the proximal vessel segments by the densities in surrounding tissue. No minimum vessel size was used for the analysis of vessel lengths. In addition, the diameters of all four main coronary branches (LMA = left main coronary artery, LAD = left anterior descending coronary artery, LCX = left circumflex coronary artery, RCA = right coronary artery) were measured on orthogonal cross-sections 5 mm from the origin using the automatically generated curved multiplanar reformations. Coronary artery diameters were compared between genders to analyze whether coronary artery size might explain gender differences in diagnostic accuracy. Coronary diameters were also compared after normalization for body surface area (in m2) determined using the formula of DuBoys and DuBoys . Finally, vessel wall calcification was compared between genders and classified visually as either no calcification, calcium spots (small isolated eccentric lesions), moderate calcification, or severe calcification (large high-density lesions extending along the vessel wall).
All data are expressed as means ± SD. A contingency analysis with a χ2 or Fisher exact test was used to compare the diagnostic accuracy of MSCT in women and men. The unpaired t-test was used to compare the examination parameters of MSCT and conventional coronary angiography, the coronary vessel lengths, noise values, and the contrast-to-noise ratios for women vs. men. The chi-square and the unpaired t-test were also used to compare nonparametric and parametric image and patient characteristics. No post-hoc power analysis was performed. A p value < 0.05 was considered statistically significant.
Coronary artery parameters
Comparison of coronary artery diameters without and after normalization for body surface area (per 1 m2) in women and men
Women (n = 50)
Men (n = 95)
3.7 ± 0.7 mm
4.6 ± 0.9 mm
3.0 ± 0.6 mm
3.6 ± 0.7 mm
2.8 ± 0.6 mm
3.2 ± 0.7 mm
3.0 ± 0.6 mm
3.6 ± 0.8 mm
After normalization for body surface area
2.1 ± 0.4 mm/m2
2.3 ± 0.5 mm/m2
1.7 ± 0.4 mm/m2
1.8 ± 0.4 mm/m2
1.6 ± 0.3 mm/m2
1.6 ± 0.4 mm/m2
1.7 ± 0.4 mm/m2
1.8 ± 0.4 mm/m2
Coronary wall calcifications
Comparison of coronary artery calcifications in women and men
Women (n = 50)
Men (n = 95)
Small calcified lesion
Small calcified lesion
Comparison of MSCT coronary angiography in women and men
Women (n = 50)
Men (n = 95)
no./total no. (%)
Negative predictive value
Positive predictive value
We observed no relevant and significant differences in other examination parameters between women and men: contrast agent amount for MSCT (107.5 ± 7.6 ml vs. 109.2 ± 11.4 ml), contrast agent amount for conventional coronary angiography (91.9 ± 13.3 ml vs. 95.8 ± 23.5 ml), room time required for MSCT (17.2 ± 3.4 min vs. 17.3 ± 6.2 min), and room time required for conventional coronary angiography (54.8 ± 11.4 min vs. 59.4 ± 17.8 min, excluding time for interventions). Also the heart rate during MSCT coronary angiography, which appears to affect CT image quality, was not significantly different between women (71.0 ± 10.0 beats/min) and men (70.0 ± 11.8 beats/min).
In this study on MSCT for coronary angiography, we found a significantly lower diagnostic accuracy and per-patient sensitivity while the nondiagnostic rate and the effective radiation dose of CT was higher for women compared with men.
In terms of image quality, it is important to compare the present image parameter results with those obtained in other studies to exclude that a potential technical insufficiency caused the differences between genders. Both the contrast-to-noise ratios and the coronary vessel lengths visualized without artifacts were similar [7, 25] or higher compared to those reported elsewhere . Moreover, no difference between the genders was observed in regards to image noise and contrast-to-noise ratios and thus, an influence is unlikely. Coronary calcium is often assumed to preclude a high diagnostic accuracy of MSCT coronary angiography, but the only comparative study thus far has found no relevant difference in diagnostic accuracy between patients with and without relevant coronary calcifications . Also calcium appears to not reduce the ability of MSCT to quanitify significant coronary stenoses . In the present study calcium was not equally distributed between the genders possible due to the difference in prevalence of disease. Despite this and in agreement with the analyses by Cademartiri et al. [27, 28] we did not find the detection of coronary artery stenoses to be significantly impaired by the presence of extensive calcifications (most of the false-negative lesions were not calcified), whereas relevant coronary calcifications were responsible for the majority of the false-positive cases in both genders.
Previous smaller studies on MSCT coronary angiography have shown no significant differences between both genders, probably because of the smaller sample sizes [20, 29]. To the best of our knowledge, the present study shows for the first time a higher diagnostic accuracy and sensitivity of MSCT for men than for women. The study is in contrast to a different analysis of 26 women that accuracy of CT coronary angiography was not significantly different from that of men . Our study is also in contrast to a recent analysis of 50 women and 50 men using 64-slice CT coronary angiography . This might be due to the improvements feasible with 64-slice CT coronary angiography [32, 33] but could also be influenced by the fact that nondiagnostic coronary segments (due to motion artifacts) which were more prevalent in women were excluded from analysis in this study  (in contrast to the intention-to-diagnose principle  used in our study).
A lower accuracy of exercise electrocardiography in women  compared with men  has already been reported in meta-analyses. Moreover, a recent comprehensive analysis of the literature suggests that women at risk or with suspected coronary artery disease are less often referred for the appropriate diagnostic test than are men . For stress testing with echocardiography and nuclear imaging, however, the evidence suggests that women, just as men, are accurately diagnosed and risk-stratified . For the symptomatic women, noninvasive stress testing is generally recommended for those at intermediate risk of coronary artery disease and stress echocardiography has similar diagnostic accuracy in women and men . However, there is an important limitation of stress nuclear imaging in the evaluation of symptomatic women – namely a higher rate of false-positive results due to breast attenuation and small left ventricular chamber sizes . Both exercise echocardiography and nuclear imaging are limited by advanced age in women with suspected disease because exercise capacity decreases with age. Thus, pharmacologic stress testing may overcome these disadvantages in many women with suspected coronary artery disease . Nevertheless, for the reasons mentioned above, testing for the presence of coronary artery disease without stress might be beneficial in women.
Two major tests have been suggested for this purpose – identification of coronary calcium on unenhanced and of coronary stenoses on contrast-enhanced CT scans. Raggi et al. recently concluded that asymptomatic women might actually benefit to a greater extent than asymptomatic men from coronary calcium scoring using computed tomography in addition to risk factor screening . However, the general clinical value of calcium scoring for both genders is still under dispute especially since large randomized studies analyzing the clinical value in management are still missing . For direct visualization of coronary stenoses, noninvasive coronary angiography using multislice CT is a potentially valuable strategy in patients with suspected coronary artery disease [2–7]. Our results, however, suggest that women might not benefit at present as much from noninvasive coronary angiography with MSCT as men do.
Despite the smaller scan range in women (smaller heart size) and a consequently shorter scan time the effective radiation dose was significantly larger in women than men, mainly as a result of the fact that the radiosensitive female breast (contributing to approximately one quarter of the dose in women) is in the x-ray path, further limiting the application of MSCT coronary angiography to female patients. In contrast to that, radiation exposure during conventional invasive angiography was not different between genders and was in the same ranges as reported previously . The higher effective dose of coronary CT angiography in women of 13.7 ± 1.2 mSv (equal to the effective dose of 100 to 150 chest radiographs or 50 to 75 bilateral mammographies) is a cause of concern because, like younger patients, females have an increased long-term cancer risk from radiation exposure . Thus the radiation risk of MSCT coronary angiography needs to be weighed against its potential clinical benefits especially in younger and female patients. However, to achieve a balanced appraisal of the radiation risks and health benefits especially in comparison to conventional coronary angiography, one must perform a net-utility analysis of life expectancy that also takes into account the short-term advantages (e.g. avoidance of the 0.11% mortality risk of invasive angiography) and clinical utility of CT coronary angiography.
Very recently 320-slice technology (single-rotation whole-heart imaging) based on acquisition of a cylindrical volume covering the entire heart has become available . This technology avoids oversampling and overranging, which cause the high radiation dose of 16- and 64-CT coronary angiography , and thereby reduces the effective dose by at least 50% as very recently demonstrated  using 256 simultaneous detector rows. Moreover, cylindrical slice CT coronary angiography using a wide-area detector (with up to 320 detector rows) also has the potential to add the fourth dimension to cardiac imaging making reliable myocardial perfusion assessment a reality. In addition to radiation exposure, clinical utility, and reduced risks also cost-effectiveness of new tests such as coronary CT angiography  and potential to triage patients  needs to be included in the societal discussion about the usefulness and utility of this ascending imaging test.
Limitations of the study
The present study is limited by its single-center design and the small number of patients (especially women) included. The prevalence and intensity (number of vessels stenosed) of coronary disease considerably varied between the genders in our study. This might have influenced the comparison of diagnostic performance. Since there is a referral bias to conventional coronary angiography with a disadvantage to women  and only patients who were referred to catheterization could be included in the present study such a bias might have also influenced our results. Upcoming multicenter studies of MSCT coronary angiography, such as the CorE64 trial, have the potential to further analyze the importance of the gender difference in noninvasive coronary angiography.
The first multicenter study on noninvasive coronary angiography with MSCT published thus far  has shown that 16-slice technology when used in several centers with varying experience is limited by a high number of uninterpretable cases and a high false-positive rate. 64-slice CT became available recently [47–52] and holds promise to increase image quality by reducing imaging time and artifacts. There is evidence from a small intraindividual study that 64-slice CT results in higher image quality for noninvasive coronary angiography than CT using 16 detector rows  and future studies will have to determine the value of 64-slice scanners in women.
Also dual-source CT has been shown to be a promising candidate to further reduce the length of the image reconstruction interval [53, 54] and thereby improve temporal resolution and might improve the results of noninvasive coronary angiography for both men and women. No beta blockers were given prior to MSCT, which might be considered a limitation since CT coronary angiography benefits from slower heart rates [55, 56]. Nevertheless, heart rate and temporal resolution were not different between genders in our study and thus are unlikely to have influenced the gender comparison of CT coronary angiography. Further improvements might be achieved in the near future using volumetric cylindrical CT coronary imaging with 256  or even 320  simultaneous detector rows. The present study limited the analysis to stenoses in segments with a reference vessel diameter of at least 1.5 mm. However, since smaller vessels are not easily amenable to coronary revascularization, all stenoses that might be targets for revascularization were included. The female patient cohort (19) that was added to our initial patient group  to increase the number of women available for comparison and thus improve scientific validity might be seen as a potential confounding factor. However, neither accuracy nor nondiagnostic rate in the initial cohort (74 and 16%) was relevantly different from the cohort of 50 women.
The results of the present study show that MSCT has a lower diagnostic accuracy and sensitivity for the detection of coronary artery disease while the nondiagnostic rate is increased in women than in men compared with conventional coronary angiography as the reference standard. Also, radiation exposure from this examination is relevantly higher in women. Thus, the potential clinical benefits of MSCT coronary angiography might not be as high for the management of women with suspected coronary artery disease as for men.
We thank Bettina Herwig for assistance in preparing and editing the manuscript.
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- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/8/2/prepub
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