1/2 Our updated meta-analysis of intravascular imaging guidance publ in JACC. Since our last synthesis in Lancet 2024, there have been 6 new RCTs with 8,670 additional pts. Total is now 28 RCTs with 24,634 patients with mean FU 22 mos. Should be enough for a definitive answer!

Hopefully just humorous technical brilliance and not the future…

One of many potential explanations….

Some things are less surprising than others. Disappointing for patients, but perhaps not surprising. Many thanks to those who set out to test plausible hypotheses.

👉Just published in @NEJM: STAREE Trial ☝️At last, robust randomized evidence on statins for primary prevention in older adults. 🔹 9,971 adults ≥70 years, without cardiovascular disease, diabetes, or dementia 🔹 Atorvastatin 40 mg vs placebo 🔹 Median follow-up: 5.9 years 🔹 Baseline LDL-C: ~127 mg/dL NEJMoa2607314.pdf 👉Key findings: 🔹 30% reduction in major cardiovascular events HR 0.70 (95% CI 0.61–0.82; P<0.001) 🔹 NNT = 37 over 5.9 years 🔹 MI: HR 0.57 🔹 Coronary revascularization: HR 0.57 🔹 Benefit was also observed in participants ≥75 years 👉Importantly: 🔹 No increase in dementia (HR 1.03) 🔹 No significant effect on all-cause mortality 🔹 No improvement in overall disability-free survival 🔹 Serious adverse events were similar between groups. ☝️Bottom line: Age alone should not be a reason to withhold LDL-C lowering. Even in healthy adults ≥70 years, lowering LDL-C translates into substantial cardiovascular benefit. @society_eas @nationallipid 🔗nejm.org/doi/full/10.1056/NE…

🫀 #REACT at #ESCCongress #Hotline How early does atherosclerosis really begin? 16,808 adults, age 18–70 without known ASCVD underwent coronary, carotid & femoral imaging 🔎 Silent atherosclerosis: 57.1% overall ➡️ Already present in ~1 in 13 adults aged 18–29 ➡️ ~9 in 10 by age 60–70! 💃🏻Women: steep rise during midlife, around menopausal transition; men developed atherosclerosis ~5–10 years earlier 🫀Atherosclerosis begins decades before clinical events—and often before conventional risk scores identify high risk. REACT should make us think about prevention much earlier Next question: can imaging-guided early intervention actually prevent progression and events? Or should we just work to prevent CVD in everyone? 📄 @NEJM nejm.org/doi/full/10.1056/NE… #ASCVD #Prevention #WomensHeartHealth #CVPrev

Recurrence of bacteraemia seems a bit of a thing. I’m running the ‘family member’ thing in my head…

This is an incredibly important study. The just presented SINGLE-AF trial randomised patients with a single risk factor (other than sex), demonstrating a significant reduction in stroke, systemic embolism, major bleeding, or death from cardiovascular causes at 24 months. Although the @SCC_CCS AF guidelines (onlinecjc.ca/article/S0828-2…) have advocated for OAC for this group of patients for many years, sometimes at contrast with other national societies, its nice to see that this approach has been validated in a large RCT. nejm.org/doi/full/10.1056/NE…

1/15 🤔Does end-stage renal disease (ESRD) make diabetes disappear? No, but in some patients with ESRD, insulin needs fall. A1c drops. Diabetes medications can be stopped. This has been called “burnt-out diabetes.” Let's examine why.

In 10,000 asymptomatic women and men, the presence of obstructive subclinical coronary atherosclerosis conferred a 4-fold and 12-fold risk of myocardial infarction. Eur Heart J by AF Larsen, KF Kofoed et al in Copenhagen General Population Study: academic.oup.com/eurheartj/a…

Reasons to do research: 1. To discover new things 2. To learn how to discover new things . . 5. To prove one can apply oneself and demonstrate willingness to complete things (not a trivial thing, but not the main point).

What’s hot, what’s not: #ESCCongress 2026 (Munich, Aug 28–31) unveils 57 trials across 12 Hot Line sessions. #Antithrombotics, #HF, #TAVI, #AF ablation all in play #CardioTwitter @escardio @DFCapodanno @Drroxmehran @DLBHATTMD @JGrapsa @mirvatalasnag @DrMarthaGulati @mmamas1973

At midnight on February 6th, earlier this year, the doorbell to our apartment rang. The doorbell was followed by a pounding on the door. I answered the door and a security person in our building handed me his phone. It was my oldest daughter Eloise. She had found my 26-year-old daughter unconscious on the floor of her apartment and had called 911. The EMT team was already there, but they did not know what was wrong with Lucy or to which hospital they would take her. I threw on some clothes and jumped in an Uber heading east toward Brooklyn. (Lucy lived alone in Williamsburg.) On the way, I learned that they were taking her to Elmhurst, a City trauma hospital in Queens. I arrived about five minutes after the ambulance to join Eloise, Lucy’s mom, and a friend, and waited to learn what was wrong. After about 15 minutes, I asked a nurse where she was. I looked over his shoulder to his computer. Next to her name, it said “non-responsive.” I walked into the emergency room and wandered around looking for her until I found her unconscious on a gurney surrounded by several doctors and nurses. By about 2:30am with the results from a CAT scan, Lucy’s doctors had determined that she had a massive brain hemorrhage and would need an emergency hemicraniectomy to release the pressure on her brain and remove the blood from the hemorrhage. I called our wonderful friend and family doctor Eddie Fisher and explained what was going on. He woke up Josh Bederson, Chairman of Neurosurgery at Mount Sinai, to find out more about Zach Hickman, the neurosurgeon on call that night. Dr. Bederson said Hickman was an excellent surgeon, which was comforting as we had no choice. The surgery to save Lucy’s life began around 3:15am and finished around 5:30am. It was successful. The following day, I joined Lucy in an ambulance while she was being transferred to Mount Sinai on Madison Avenue. Later that day, we determined from Lucy’s Oura ring that her hemorrhage had occurred around 9am, which meant that more than 19 hours had passed from the time of the hemorrhage to the completion of the surgery to release the pressure on her brain (I only wish @ouraring had an alert for this kind of a medical event. Imagine it could call a family member if the wearer doesn’t cancel the alert). I later learned that the standard of care is not to do surgery to save a patient with a large brain bleed if more than five hours have passed since the hemorrhage. Even when the surgery is done, I was told that the likely outcome for the patient is a few months in a nursing home and death from pneumonia. When I met Lucy’s doctors, I did my best to inspire them: “Let’s see what can be accomplished if we give her the best care possible and we invest unlimited resources to restore her to life.” And I promised that whatever we learned we would make available to everyone. Dr. Chris Kellner, her neurosurgeon, and Dr. David Putrino, Director of Rehabilitation Innovation for the Mount Sinai Health System have led Lucy’s care team since that day. Words cannot describe the remarkable and compassionate care that she has received beginning with the EMT team and then from nurses, doctors, therapists, and the army of people who have worked to save her and return her to life. To this day, we have a daily Zoom where we discuss her progress and make adjustments to her care. While her care and oversight have been incredible, the learnings for the Mount Sinai team have also been elucidating and will assist in the care of many others. Lucy began in a bad place. She was in a coma for several weeks and then awoke not being able to breathe on her own, unable to walk, see or speak. Over the last six months, she has recovered her cognition – she understands everything including her circumstance – is able to walk a hundred or more steps at a time with assistance, is making progress with sounds, vowels and consonants and the beginnings of speech, but she remains unable to see. Each day, she makes a little progress, and daily progress compounds. Every day I tell her that she just needs to make a little progress and it won’t be long before she is back. We remain optimistic that Lucy will return to normal function. It will likely take years, but I believe it is only a matter of time, hard work, and technological progress, along with some, and perhaps a lot, of divine intervention. Many people have been praying for Lucy and we are incredibly grateful for the prayers and remarkable support she has received. Lucy’s friends have been with her every day since the beginning, and their presence and friendship have saved her life and helped to rebuild and maintain her spirit. And on a very positive note, Lucy’s challenge has brought together our entire modern family who have all been incredibly devoted to her care and recovery. Lucy's vision and other faculties may require some form of brain computer interface, work that is underway at Neuralink, Precision Neuroscience, Science, Synchron, Nudge, and other companies in the space. If you are going to have a devastating brain injury, now is the best time in history for that to happen. We are living in a world when you can be confident that the blind will soon see again. We are going to do everything we can to help make that happen, including by assisting existing companies in the space. With respect to our promise to make Lucy’s care available to others, we have made good progress. In May, a real estate colleague made me aware of a 93% vacant, brand new, 400,000 square foot Class A+ purpose-built biotech facility on West End Avenue between 65th and 66th Streets that missed the market and was available for sale. The Pershing Square Foundation acquired the building 60 days later. We also put under contract an adjoining 130,000 square foot building at 320 West 66th Street that is currently being used by Saturday Night Live for studio space. The building has 35-foot ceilings with massive column-free spaces that can be converted into superb rehabilitation facilities. We will close on the SNL building in December. We are also acquiring an adjoining vacant lot with additional air rights. With just the existing zoning rights, we can add a 150,000 square feet for a total of 680,000 square feet, a lab footprint larger than Rockefeller University, and that’s without including the potential for an upzoning that would allow for substantially more buildable area on the site’s 3.4 acres with spectacular views of the Hudson. Our goal is to build the world’s greatest brain research, rehabilitation, recovery, human optimization, and longevity institute. We have named it The Ackman Oxman Institute or the AOI for lack of a better name, but also to reinforce the point that Neri and I and our family are all-in on the mission. The AOI will be patient-centric. It will not be an academic research institute that produces lots of papers, a Nobel Prize winner or two, but little if any results for patients. We will be laser-focused on cures, treatments, devices, rehabilitation and exercise equipment, and targeted and basic research with a goal of massively accelerating the time from idea to innovation to production to helping a patient. While the AOI will be a non-profit, it will have highly commercial instincts. The AOI will have its own venture funding and will work to develop innovations to create companies that we will seed, assist, and spinout to ensure technologies, treatments, techniques, and drugs get to patients as promptly as possible. On one 3.4 acre campus in what is still the greatest city in the world, we will do neurosurgery, neuroscience, rehabilitation, nutrition, BCI and device development, human trials, hyperbaric oxygen treatments, and life extension programs, and we will mandate and incentivize collaboration among the teams with no silos, politics, bureaucracy, or any other constraint that is inconsistent with the mission. Mount Sinai will be an important partner and deservedly so, but it won’t be our only hospital or medical school partner as we don’t believe any institution has a monopoly on the best ideas or the best talent. We don’t believe in exclusive relationships because that is not in the best interest of patients. Five years ago, we considered launching a brain institute inspired by Neri’s mom who sadly died from Alzheimer’s. We couldn’t make the math work as the real estate was too expensive and we believed it would be too difficult to recruit the best talent from universities to our effort. Since then, the real estate became available at a 70% discount, universities became a much less attractive place to work due to politics outweighing meritocracy, protests that disrupt learning, the curse of antisemitism, and a decline in funding. Fortunately, during the same time, I made sufficient personal economic progress to make the AOI possible. The advance of AI in the last few years will also enable us to greatly accelerate our mission. AI still has a lot to learn about human intelligence and the brain, and the AOI should be at the forefront of the interplay between the brain and AI. Today, I am making a public filing disclosing a gift from Neri and me of ~$400 million or 10,000,000 shares of Pershing Square Inc. (PS) to the AOI. It is very early days for Pershing Square so these shares are intended to anchor the long-term work of the AOI as the shares compound over time while generating what we expect will be a growing stream of quarterly dividends to fund the Institute. We will also be announcing an additional gift of similar and potentially greater size which won’t be in the form of Pershing Square stock to provide the AOI with the short- and intermediate-term runway necessary to enable it to achieve its goal of becoming a self-sustaining institute, which reinvests all of its revenues, royalties, and the economic rewards of company formation to advance the fields of brain health and human longevity. Neri and I have chosen to anchor the funding of the AOI to maintain vision alignment and limit the need for the organization to focus on fundraising. We expect the AOI to be the best-resourced brain, rehab, recovery, and longevity institute in the world. We are grateful to have been able to form a board which includes Dean Kamen (our generation’s Thomas Edison), George Yancopoulus (CEO of Regeneron), James Rothman (Nobel Laureate), Bernardo Sabatini (neuroscientist), Chris Kellner (neurosurgeon), Olivia Flatto (CEO Pershing Square Foundation), Neri Oxman, and myself. We have recently identified a CEO who we expect to announce by October along with other key hires, and are beginning searches for a Chief Scientific Officer, a Chief AI/Technology Officer, a Chief Operating Officer, a Chief Financial Officer, and other key leadership roles. If you find what we are building compelling and want to be part of the leadership team that creates and builds the AOI from a standing start, please send an email to: search@aoiinst.org with a short note as to why you believe you can help. Please include your best three ideas for the AOI along with a summary of your background and your most important accomplishments. We promise strict confidentiality to those expressing interest in working with us. We have learned from Lucy that the brain can recover from even catastrophic injury. There is so much more work to be done as the mind is a terrible thing to waste. For details from my Pershing Square SEC filing see: sec.gov/Archives/edgar/data/…

‼️ The most anticipated trial of the year #ZEUS IL-6 inhibitor ziltivekimab does not reduce MACE in >6,300 people with ASCVD, CKD, and inflammation hazard ratio 0.99; 95% confidence interval 0.88 to 1.11 uk.finance.yahoo.com/news/no…

This video comes up every 50 posts on my timeline and every time I think at some point they are not going to surface. Amazing strength and bravery.

75 YEARS AND THE WAIT IS OVER!!!!! MAYO ARE FINALLY ALL-IRELAND FOOTBALL CHAMPIONS!!!!!! 📺 Watch on RTÉ2 and RTÉ Player 📻 Listen on RTÉ Radio 1 #SundayGame

Mark Knopfler 🎼A Night In London, 1996 (Full Concert)🎵 Mark Knopfler makes music in the most emotional way, so please listen to this wonderful live performance :) 94 minutes live 🎼❤️

Not a good advert for football, but the best managed team in the tournament won. I suspect the repercussions of this most unusual tournament will not fade fast.

This is cool. Anyone who has played an instrument will enjoy this. Charisma and intuitive talent: piped.video/L3eDYLmHaS4?si=jp4C… Forensic learner: piped.video/sHU4re5lOpE?si=xFeX…