TheFa(c)tHunter

👉 Metabolic Disorders and Cardiovascular Disease: Key Insights 👆 A recent ESC scientific statement highlights the central role of metabolic dysfunction in cardiovascular disease and the therapeutic implications of emerging cardiometabolic therapies. 👆 Key points: 📍 Cardiovascular disease is increasingly driven by metabolic dysfunction—obesity, type 2 diabetes, and dyslipidaemia act synergistically to accelerate atherosclerosis, heart failure, and arrhythmias. 📍 Metabolic disease disrupts myocardial energetics, promoting metabolic inflexibility, mitochondrial dysfunction, oxidative stress, and lipotoxicity. 📍 Modern cardiometabolic drugs provide benefits beyond glucose lowering. SGLT2 inhibitors and GLP-1–based therapies improve cardiovascular outcomes through pleiotropic mechanisms. 📍 Atherogenic risk extends beyond LDL-C, with triglyceride-rich lipoproteins and Lp(a) contributing to residual cardiovascular risk. 📍 Future progress will require a systems-biology approach, integrating multi-organ mechanisms, multi-omics data, and translational research. 👆 Bottom line: Cardiovascular disease should increasingly be understood as a systemic cardiometabolic disorder rather than an isolated vascular pathology. 🔗 Open Access academic.oup.com/eurheartj/adva… @society_eas @escardio

I feel like I can breathe again! Get ready for a rant I've been waiting to let loose for a year. 🔥 First, here are the core facts about the Keto-CTA study to date: 🚨PART 1: THE FACTS 👉From its inception, Dave, Adrian, and I, being associated via the funding body (the Citizen Science Foundation), were blinded to certain elements of the data. The purpose was to protect the integrity of the project. 👉The profound irony is this also meant that, prior to publication, we couldn’t perform certain ‘checks’ and had to trust others to do so. Speaking for myself, it’s now painfully clear that was a mistake. 👉However, after the April 7th paper was published, "anomalies" (if I’m being polite) were noted with the Cleerly scans. 👉 Cleerly refused to redo the scans, despite multiple requests and being offered payment. 👉Importantly, and to my dismay, the original Cleerly reads were UNBLINDED, introducing a major source of bias. 👉At additional expensive, the scans were rerun through HeartFlow in a properly blinded analysis, and via the pre-specified QAngio methodology. 👉HeartFlow and QAngio agreed with each other and were discordant with the Cleerly analysis. 🚨PART 2: THE NEW NEWS What happened next was brilliant! And, truth be told, I only found out about it yesterday. For my own legal security – and at the recommendation of my friend and colleague who was taking the worst of it on the back end – there was a lot I didn’t know until this point. This is what happened… 👉Several participants independently submitted their scans to Cleerly as a workaround to obtain a truly blinded Cleerly analysis. 👉Those results were highly discordant with the original Cleerly analysis and aligned with the HeartFlow and QAngio analyses. The difference between the original Cleerly scans and the repeated blinded scans was massive! The original unblinded analysis reported a +20.9 mm³ mean increase in non-calcified plaque volume, while the blinded repeats showed a -5.1 mm³ mean decrease. I mean, MY GOODNESS!!! I basically did a backflip when I found out (@realDaveFeldman can release the footage of the meeting at his discretion) If you’ve been following the KETO-CTA story up to this point, the consistency of the findings across HeartFlow, QAngio, and now Cleerly itself (based on the blinded reads) should bring much-needed clarity. The converging results fundamentally reshape the narrative and directly refute the claim that the study demonstrates massive, unprecedented plaque progression in LMHR and near-LMHR And, after all that, the fact remains that every single analysis found no association between ApoB levels or LDL exposure and plaque progression. LET ME REPEAT: And, after all that, the fact remains that every single analysis found no association between ApoB levels or LDL exposure and plaque progression. 🚨 PART 3: NEXT STEPS In terms of next steps, I’ll quote my colleague Dave: “we have already taken steps regarding last year’s paper that contained the original Cleerly analysis.” I’ll leave it at that for now so I don’t overstep. But let me say, that’s the highly polished and diplomatic version. I certainly have stronger words about this process, but perhaps now is not the time. Where I will speak more plainly is in regard to the behavior of some detractors over the past several months. In a few cases, I’ve reached out privately to individuals who should know better, gently suggesting that, in light of the new evidence (Heartflow and QAngio), it might be time to reassess or lighten the abuse. For anyone sincerely paying attention—and for anyone with even modest insight into how scientific bureaucracy works—I hope it is now clear why we were not more forthcoming earlier in the process. 👉And trust me when I say, it’s never been harder to keep my mouth shut about anything in my life. I've accumulated more cortisol AUC in the last 11 months then in the entirety of my life to age 29. 🚨PART 4: SPEAKING FOR MYSELF Speaking for myself, I have been beyond frustrated and disappointed. At multiple stages, it has become painfully—and increasingly—clear to me that our scientific system, which presents itself as purely meritocratic, is far more political than most would imagine. These are difficult words for me to say as someone who comes from a family of doctors and scientists and who has spent his entire career in academic institutions—multiple Ivy League universities @Harvard @dartmouth, two doctorates, and top-ranked institutions in both England @UniofOxford and the United States. I was groomed in conventional academic medicine. If I have any bias, it’s to see the best in conventional medicine and modern scientific process. Most of my loved ones have made their living within this ecosystem. But when you pull back the curtain, the reality can be sobering. To those detractors who have verbally abused or personally attacked my colleagues and me—perhaps out of naivete or ignorance—I will say this plainly: it’s time to check yourselves. Too many people have spoken out of turn, seemingly to score points rather than to engage thoughtfully with an evolving scientific story—one that has been evolving for quite some time. When the HeartFlow and QAngio analyses were released, that alone should have prompted serious reflection. At minimum, it should have raised questions. The subsequent silence from some of the loudest critics, after they believed they had “won” a round, is telling. Science deserves better than scorekeeping. It deserves intellectual honesty and the humility to update one’s position when new evidence emerges. At times over the last year, the lack of curiosity, sincerity, and intellectual honesty from people who I tried to give the benefit of the doubt has made me want to vomit. And trust me when I say, this isn’t a victory lap. This is a promise. We are now over a hurdle that I have been waiting for almost a year. And frankly, I am ready to run headfirst through brick walls with my colleagues and friends by my side — those whom I trust to pursue the hard questions and the honest answers — and do so indefinitely using the tools and resources at our disposal, even when, and especially when, the scales are improperly tilted against us. Lucky for us, the intellectual environment is expanding — the black box of academia beginning to crack open. So someone hand me a crowbar, because I’m committing myself fully and completely, over the coming years and decades, to prying it wide open. Not gently. Not quietly. But decisively. My final words of this verbose dissertation? LFG

@sibaburck Scientific evidence: aleph2020.org/planet/greenho…