{"id":10801,"date":"2025-09-16T15:59:01","date_gmt":"2025-09-16T22:59:01","guid":{"rendered":"https:\/\/cholesterolcode.com\/?p=10801"},"modified":"2025-09-16T15:59:06","modified_gmt":"2025-09-16T22:59:06","slug":"keto-cta-update","status":"publish","type":"post","link":"https:\/\/cholesterolcode.com\/keto-cta-update\/","title":{"rendered":"Keto-CTA Preliminary Data Update"},"content":{"rendered":"\n<p>It&#8217;s been a little while since the release of our April 7th paper for the Keto-CTA study and news on<br>our documentary around it, <a href=\"http:\/\/cholesterolcodemovie.com\">The Cholesterol Code<\/a>. I wanted to wait until all four analyses were in before doing a full update here on the blog.<\/p>\n\n\n\n<figure class=\"wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\n<span class=\"embed-youtube\" style=\"text-align:center; display: block;\"><iframe loading=\"lazy\" class=\"youtube-player\" width=\"796\" height=\"448\" src=\"https:\/\/www.youtube.com\/embed\/aJobOSRdIOM?version=3&#038;rel=1&#038;showsearch=0&#038;showinfo=1&#038;iv_load_policy=1&#038;fs=1&#038;hl=en-US&#038;autohide=2&#038;wmode=transparent\" allowfullscreen=\"true\" style=\"border:0;\" sandbox=\"allow-scripts allow-same-origin allow-popups allow-presentation allow-popups-to-escape-sandbox\"><\/iframe><\/span>\n<\/div><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\">INITIAL CONTROVERSY<\/h3>\n\n\n\n<p>Interestingly, since April, critics have asserted our study wasn\u2019t detecting an association<br>between LDL cholesterol and plaque progression because &#8220;everyone had high LDL.&#8221; As<br>one prominent critic put it, &#8220;All of these people had high LDL and high ApoB.&#8221;<\/p>\n\n\n\n<p>This criticism assumes we had a narrow range of LDL levels\u2014something like a<br>standard deviation of, say, 10 mg\/dL clustered tightly around our mean of 253 mg\/dL. If<br>that were true, I&#8217;d agree the criticism would be valid.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/www.jacc.org\/doi\/10.1016\/j.jacadv.2025.101686\"><img loading=\"lazy\" decoding=\"async\" width=\"935\" height=\"1024\" src=\"https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/keto-cta-table-1-935x1024.jpg\" alt=\"\" class=\"wp-image-10802\" srcset=\"https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/keto-cta-table-1-935x1024.jpg 935w, https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/keto-cta-table-1-274x300.jpg 274w, https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/keto-cta-table-1-768x841.jpg 768w, https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/keto-cta-table-1-796x872.jpg 796w, https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/keto-cta-table-1.jpg 945w\" sizes=\"auto, (max-width: 935px) 100vw, 935px\" \/><\/a><\/figure>\n\n\n\n<p>But our actual spread was already published in <a href=\"https:\/\/www.jacc.org\/doi\/10.1016\/j.jacadv.2025.101686\">Table 1 of our paper<\/a>. That table points<br>out that we had a standard deviation of 84.7 mg\/dL and an interquartile range of 202 to<br>308 mg\/dL. Our participants&#8217; LDL cholesterol levels ranged from 49 mg\/dL at the lowest<br>to 591 mg\/dL at the highest\u2014a spread of 542 mg\/dL.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"576\" src=\"https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/keto-cta-ldl-c-spread-1024x576.png\" alt=\"\" class=\"wp-image-10803\" srcset=\"https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/keto-cta-ldl-c-spread-1024x576.png 1024w, https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/keto-cta-ldl-c-spread-300x169.png 300w, https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/keto-cta-ldl-c-spread-768x432.png 768w, https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/keto-cta-ldl-c-spread-1536x864.png 1536w, https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/keto-cta-ldl-c-spread-796x448.png 796w, https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/keto-cta-ldl-c-spread.png 1920w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n\n\n\n<p>I&#8217;m going to make what some might consider an audacious statement: I&#8217;m confident we<br>have the largest spread of LDL cholesterol of any prospective imaging study ever<br>conducted. I wasn\u2019t able to find anything even close to comparable.<\/p>\n\n\n\n<p>This matters because the lipid hypothesis itself is built on dose-dependent relationships.<br>As the <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/28444290\/\">2017 European Atherosclerosis Society consensus statement<\/a> puts it: the<br>probability of plaque development &#8220;increases in a dose dependent manner&#8221; and is<br>&#8220;proportional to both the absolute magnitude and duration of exposure to elevated LDL<br>cholesterol.&#8221;<\/p>\n\n\n\n<p>The dose-dependent, log-linear relationship between LDL and atherosclerosis isn&#8217;t a<br>movable goalpost\u2014it <strong><em>IS<\/em><\/strong> the lipid hypothesis. We had the dose variation. We had the<br>range. The association simply wasn&#8217;t there.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">THE CLEERLY SITUATION<\/h3>\n\n\n\n<p>So why weren&#8217;t we more vocal about defending our work? The answer lies in what was<br>happening behind the scenes with our data analyses.<\/p>\n\n\n\n<p>Remember: <em>the scans are the scans are the scans<\/em>. All our analyses\u2014semi-quantitative,<br>Cleerly, HeartFlow, and QAngio\u2014looked at the exact same 200 CT scans from our 100<br>participants.<\/p>\n\n\n\n<p>When I received access to the raw Cleerly data on April 18th, eleven days after<br>publication, I found several concerning issues. I brought these to the attention of both<br>Lundquist and Cleerly immediately. In an April 24th meeting, Cleerly&#8217;s then-CMO, who was also a co-author on our paper, agreed these were important concerns and<br>committed to running a blinded quality control pass to confirm or disconfirm the results.<br>However, what followed surprised us. The previous commitment was disregarded, and Cleerly asserted they would not follow through on the blinded quality control pass.<\/p>\n\n\n\n<p>At that point, we knew we needed to engage another independent, AI-guided CTA analysis service.  This is what brought us to look into Heartflow.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">MULTIPLE INDEPENDENT CONFIRMATIONS<\/h3>\n\n\n\n<p>Under normal circumstances, when two analyses disagree, adding a third to break the tie would be fairly standard. But these weren&#8217;t normal circumstances. Many long time critics had become quite attached to the Cleerly analysis, and thus we wanted to add an additional blinded, independent confirmation to help us all get a stronger redundancy for confirmation.<\/p>\n\n\n\n<p>Now, here are the results. For absolute change in non-calcified plaque volume\u2014the<br>numbers that matter most\u2014Cleerly showed 18.8 mm\u00b3, while HeartFlow showed 5.5<br>mm\u00b3 and QAngio showed 5.6 mm\u00b3. HeartFlow and QAngio were in close agreement<br>with each other, but both disagreed substantially with Cleerly.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">VERIFIED REGRESSION<\/h3>\n\n\n\n<p>Here&#8217;s the exciting part. Both HeartFlow and QAngio showed substantial numbers of<br>participants with non-calcified plaque regression\u201433 regressors for HeartFlow and 15<br>for QAngio in non-calcified plaque volume. More importantly, Dr. Budoff and his team at<br>Lundquist have independently verified this regression in a subset of these participants<br>by direct visual inspection of the scans.<\/p>\n\n\n\n<p>This slides was taken directly from my presentation:<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"527\" src=\"https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/regression-1024x527.png\" alt=\"\" class=\"wp-image-10805\" srcset=\"https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/regression-1024x527.png 1024w, https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/regression-300x154.png 300w, https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/regression-768x395.png 768w, https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/regression-1536x790.png 1536w, https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/regression-796x410.png 796w, https:\/\/cholesterolcode.com\/wp-content\/uploads\/2025\/09\/regression.png 1821w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\">FINAL THOUGHTS<\/h3>\n\n\n\n<p>Needless to say, it\u2019s been exciting to see all these data come together.<\/p>\n\n\n\n<p>Across multiple independent analyses\u2014and with direct confirmation from one of the world\u2019s leading cardiology imaging teams\u2014the results have remained consistent: the predicted dose-dependent relationship between LDL cholesterol and plaque progression simply did not appear.<\/p>\n\n\n\n<p>It\u2019s worth underscoring that, yes, there is a subset of rapid progressors, as you\u2019d expect in any middle-aged population. But even here, progression shows no association to LDL cholesterol; in fact, some progressors had levels lower than the cohort average.<\/p>\n\n\n\n<p>Conversely, we observed clear evidence of <strong><em>regression<\/em><\/strong> in another subset of participants, including some with much higher than average LDL cholesterol\u2014indeed, some with extremely high levels. (We\u2019ll expand more on this in our upcoming paper.)<\/p>\n\n\n\n<p>There\u2019s still much more work ahead, and I look forward to sharing future announcements. For now, I want to thank each and every one of you for your tremendous support\u2014it\u2019s been essential to moving this research forward.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>It&#8217;s been a little while since the release of our April 7th paper for the Keto-CTA study and news onour documentary around it, The Cholesterol Code. I wanted to wait until all four analyses were in before doing a full update here on the blog. INITIAL CONTROVERSY Interestingly, since April, critics have asserted our study &hellip; <\/p>\n<p><a class=\"more-link btn\" href=\"https:\/\/cholesterolcode.com\/keto-cta-update\/\">Continue reading<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[1],"tags":[],"class_list":["post-10801","post","type-post","status-publish","format-standard","hentry","category-uncategorized","item-wrap"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p9EmAp-2Od","_links":{"self":[{"href":"https:\/\/cholesterolcode.com\/wp-json\/wp\/v2\/posts\/10801","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cholesterolcode.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cholesterolcode.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cholesterolcode.com\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/cholesterolcode.com\/wp-json\/wp\/v2\/comments?post=10801"}],"version-history":[{"count":2,"href":"https:\/\/cholesterolcode.com\/wp-json\/wp\/v2\/posts\/10801\/revisions"}],"predecessor-version":[{"id":10806,"href":"https:\/\/cholesterolcode.com\/wp-json\/wp\/v2\/posts\/10801\/revisions\/10806"}],"wp:attachment":[{"href":"https:\/\/cholesterolcode.com\/wp-json\/wp\/v2\/media?parent=10801"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cholesterolcode.com\/wp-json\/wp\/v2\/categories?post=10801"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cholesterolcode.com\/wp-json\/wp\/v2\/tags?post=10801"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}