{"id":1044,"date":"2016-05-06T14:10:40","date_gmt":"2016-05-06T14:10:40","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=1044"},"modified":"2017-08-21T10:55:05","modified_gmt":"2017-08-21T10:55:05","slug":"primary-care-corner-with-geoffrey-modest-md-femalemale-differences-in-noninvasive-cardiac-testing","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/05\/06\/primary-care-corner-with-geoffrey-modest-md-femalemale-differences-in-noninvasive-cardiac-testing\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: Female\/Male Differences in Noninvasive Cardiac Testing"},"content":{"rendered":"<p><strong>By Dr. Geoffrey Modest<\/strong><\/p>\n<p>Subgroup analysis of the PROMISE trial found a significant difference in prognostic information in women vs men by the type of cardiac\u00a0test done\u00a0(see\u00a0DOI: 10.1016\/j.jacc.2016.03.523).\u00a0For my review of the PROMISE trial overall, see\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/03\/22\/primary-care-corner-with-geoffrey-modest-md-coronary-angiography-or-exercise-testing-for-chronic-angina\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/03\/22\/primary-care-corner-with-geoffrey-modest-md-coronary-angiography-or-exercise-testing-for-chronic-angina\/<\/a>\u00a0, which includes my concerns about radiation exposure as well as what defines\u00a0the gold standard to evaluate sensitivity\/specificity.<\/p>\n<p>Details:<\/p>\n<ul>\n<li>In the original PROMISE trial, 10,003 outpatients with stable symptoms suggestive of CAD were randomized to a\u00a0functional test (a stress test, as chosen by the clinician: exercise ECG, stress echo, or stress nuclear)\u00a0vs anatomic test\u00a0(computed tomographic angiography &#8211;\u00a0CTA), followed 25 months, and investigators\u00a0found no difference in outcomes.\u00a0The current analysis looked at the prognostic capabilities of the different non-invasive tests by sex.<\/li>\n<li>8966 patients (53% women,\u00a0mean age 60, 22% ethnic minority, 65% hypertension, 21% diabetes, 37% metabolic syndrome, 68% dyslipidemia, 50% current\/former smoker, BMI 30, Framingham risk score 15% in women\/29% in men, 75% presented with chest pain though 78% of them were felt to be &#8220;atypical&#8221;) who received a\u00a0noninvasive test with interpretable results<\/li>\n<li>CTA was performed in 4500 (52% of the\u00a0women) and stress testing in 4466 (53% of the\u00a0women)<\/li>\n<li>A positive CTA was if there were\u00a0 \u226570% stenosis in at least one epicardial artery or \u226550% stenosis in the left main<\/li>\n<\/ul>\n<p>Results:<\/p>\n<ul>\n<li>456 women had a positive result (9.7%) but a\u00a0significantly smaller proportion of positive CTAs vs stress tests: adjusted OR of 0.67 (0.55-0.82, p&lt;0.001), and the CTA had many fewer positive results\u00a0vs\u00a0the exercise ECG (OR 0.39), less so for nuclear stress test (OR=0.66), and was not significant for stress echo (OR=0.90)<\/li>\n<li>640 men (15.1%) had a positive test, with marginally greater proportion of CTAs being positive (16% vs 14%, p=0.047). Men were more likely to have a positive CTA vs stress test with adjusted\u00a0OR 1.23 (1.04-1.47, p=0.019); CTA had more positive results\u00a0than an exercise ECG (OR=1.79), or stress echo (OR=2.10) but was\u00a0not different from a nuclear stress test (OR=1.03)<\/li>\n<li>In terms of <strong>clinical outcomes over 25 months<\/strong> (primary endpoint being:\u00a0a\u00a0composite of\u00a0all-cause death\/MI\/hospitalization for\u00a0unstable angina)\n<ul>\n<li>Overall a positive noninvasive did strongly predict\u00a0a primary endpoint<\/li>\n<li>112 women (2.4%)\u00a0had primary endpoint:\u00a0a positive\u00a0CTA was more than 2x as\u00a0predictive as a positive stress test (adjusted\u00a0HRof 5.86 vs 2.27)<\/li>\n<li>153\u00a0men\u00a0(3.6%)had primary endpoint:\u00a0a positive CTA was nonsignificantlyweaker than a positive stress test (adjusted HR of 2.80\u00a0vs 4.42).<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>So, a\u00a0few points:<\/p>\n<ul>\n<li>It has been known for a long time that women have more false positive stress tests. This has been attributed to smaller coronary vessel size, higher prevalence in microvascular coronary dysfunction in women, baseline differences in resting ECG, breast attenuation for some of the tests.<\/li>\n<li>In terms of risk stratification, CTA yields better prognostication over stress tests (i.e. women with a positive CTA tended to do worse than if they had\u00a0a positive stress test); men get pretty much the same by\u00a0either modality (trend to doing better with a positive stress test).<\/li>\n<li>But the difference in women\u00a0could be because\u00a0women do have more microvascular heart\u00a0disease which is missed on a CTA, and\u00a0microvascular coronary dysfunction\u00a0has a better prognosis and may not lead to many events in the short 25 month follow-up of this study; i.e., CTA may be prognostically\u00a0better than functional tests, at least in the short-term, since it picks up more imminent clinical events.\u00a0But if the treatment is the same for any positive test\u00a0(aggressive risk factor reduction), one might imagine that a normal\u00a0CTA could have the very negative impact of leading to less aggressive treatment by the clinician\/less follow-through by women (&#8220;after all, it was a negative test, so I must be fine&#8221;). I.e., the higher positivity rate of the functional stress tests (&#8220;false positives&#8221;)\u00a0could well lead to better long-term outcomes [it is not really clear what the gold standard is. Is it really a false positive if a woman has very real\u00a0microvascular heart disease but it takes longer to manifest itself as clinical cardiac events?]<\/li>\n<li>There are, of course, several concerns in interpreting the above. This is a secondary analysis of a large pragmatic trial, so there can always be unexpected confounders. Also, as a pragmatic trial, there was no systematic randomization to different types of stress tests, and no control over therapies after a positive test (g., did those women with a positive CTA get different treatments, pharmacologic or invasive, which might explain the different prognostic value\/future events?).\u00a0(I should also note\u00a0there was no cardiac\u00a0cathconfirmation of CAD, though I would argue that\u00a0this is not an uncontested gold standard,\u00a0as noted in\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/03\/22\/primary-care-corner-with-geoffrey-modest-md-coronary-angiography-or-exercise-testing-for-chronic-angina\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/03\/22\/primary-care-corner-with-geoffrey-modest-md-coronary-angiography-or-exercise-testing-for-chronic-angina\/<\/a>\u00a0).<\/li>\n<\/ul>\n<p>This study reinforces that<strong> there are significant differences in heart disease\u00a0between men and women<\/strong>, as manifested by the differences in imaging sensitivities as above. I do not think this trial shows conclusively which test should be done\u00a0and, importantly, there was no information about how those with positive tests were treated.\u00a0But I bring this up since it does reinforce that there are significant differences in the pathophysiology and testing for men and women. I will add the following from a more EBM focus (though 3 years old now):<\/p>\n<p><a href=\"http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK153207\/pdf\/Bookshelf_NBK153207.pdf\">http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK153207\/pdf\/Bookshelf_NBK153207.pdf<\/a> is the AHRQ evaluation of noninvasive technologies for\u00a0the diagnosis of CAD in women, released Feb 2013,\u00a0which notes that:<\/p>\n<ul>\n<li>Exercise EKG: 41 studies, high strength of evidence, sensitivity 62%, specificity 68%<\/li>\n<li>Exercise\/stress echo: 22 studies, high strength of evidence, sensitivity 79%, specificity 83%<\/li>\n<li>Exercise\/stress\u00a0radionucleide: 30 studies, high strength of evidence, sensitivity 81%, specificity 78%<\/li>\n<li>CTA: 8 studies, low strength of evidence, sensitivity 93%, specificity 77%<\/li>\n<li>And they noted overall that in women, stress ECG and CTA were both less sensitive and less specific than in men, with stress ECG being statistically significantly less specific than the other noninvasive modalities<\/li>\n<li>Their bottom line:\n<ul>\n<li>In women with no known CAD, the specificity of stress EKG was less than stress echo<\/li>\n<li>Though there is higher radiation exposure levels in women over menwith CTA (3 of 4 studies), there is not enough info in the literature about relative radiation exposures, or other safety concerns<\/li>\n<\/ul>\n<\/li>\n<li>So, as per usual, this detailed analysis raised more questions than it answered, including: the\u00a0risks of noninvasive testing (including radiation), the\u00a0comparative accuracy in real-world setting, the\u00a0best sequential order of these tests (including by differing pre-test probabilities), or if there\u00a0are other population differences besides male\/female (race\/ethnicity, for example), etc.<\/li>\n<\/ul>\n<p>So, my bottom line at this point is pretty much unchanged: I usually get a stress echo in women, especially since there are so many &#8220;false positives&#8221; with regular exercise testing, it is a functional vs anatomic test (which, it seems to me, is more likely to reflect the real\u00a0effect of the cardiac disease on the individual patient),\u00a0and since there is no radiation exposure. (Echo\u00a0also gives collateral information about cardiac functioning, LVH, valves, etc., which might be useful clinically). And the above large but perhaps only marginally useful PROMISE study does seem to reinforce that stress echos seem closest to their strongest candidate of CTA (though, unfortunately, their clinical outcome data did not allow statistically\u00a0for\u00a0breakdown of outcomes by\u00a0the different types of\u00a0stress testing by modality)<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Primary Care Corner with Geoffrey Modest MD: Female\/Male Differences in Noninvasive Cardiac Testing [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/05\/06\/primary-care-corner-with-geoffrey-modest-md-femalemale-differences-in-noninvasive-cardiac-testing\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":148,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[14283],"tags":[],"class_list":["post-1044","post","type-post","status-publish","format-standard","hentry","category-archive"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1044","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/users\/148"}],"replies":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/comments?post=1044"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1044\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/media?parent=1044"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/categories?post=1044"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/tags?post=1044"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}