Sex and gender differences in coronary pathophysiology and ischaemic heart disease: do not miss the new collaborative scientific statement published in the current Journal issue. doi.org/10.1093/eurheartj/eh… #IHD #CAD #cardiotwitter @ESC_Journals @escardio

Top 10 Learnings from ADA 2026, (6-8 June) ADA 2026: 🔟 CME INDIA Clinical Pearls 1️⃣ Oral GLP-1 therapy is becoming a serious clinical reality. Orforglipron, a daily oral non-peptide GLP-1RA, added to basal insulin in long-standing T2D reduced HbA1c by 1.54–2.05% and body weight by 2.7–6.1%, without increasing overall hypoglycaemia risk. 👉 Clinical message: Oral GLP-1RA may become a practical intensification option before prandial insulin. 2️⃣ Orforglipron outperformed dapagliflozin in metformin-treated T2D. In ACHIEVE-2, orforglipron showed superior HbA1c reduction versus dapagliflozin; higher doses also improved weight, triglycerides, non-HDL-C and systolic BP. ⚠️ GI adverse events remain the key limitation. 3️⃣ CagriSema may change basal insulin add-on strategy. Cagrilintide–semaglutide added to basal insulin reduced HbA1c by around 2.1–2.33%, with 10–12% weight loss and no severe hypoglycaemia. 👉 Pearl: Insulin-treated T2D need not always mean weight gain. 4️⃣ Retatrutide was the metabolic showstopper of ADA 2026. In TRANSCEND-T2D-1, retatrutide monotherapy reduced HbA1c by up to 1.94% and body weight by up to 15.3% in early T2D. 🔥 Triple agonism—GIP, GLP-1 and glucagon—may be the next major leap. 5️⃣ Semaglutide 7.2 mg may offer weight loss plus kidney-inflammatory benefit. In STEP UP post hoc analysis, semaglutide 7.2 mg and 2.4 mg preserved kidney function by creatinine–cystatin C eGFR and reduced hsCRP. 🧠 Caution: Post hoc data, but biologically and clinically interesting. 6️⃣ Tirzepatide did not worsen retinopathy despite powerful HbA1c reduction. In SURPASS-CVOT retinopathy substudy, tirzepatide lowered HbA1c more than dulaglutide, but did not meaningfully worsen diabetic retinopathy at 12 months. 👁️ Clinical pearl: Eye screening remains essential, but retinal safety looks reassuring. 7️⃣ Finerenone moved beyond diabetic kidney disease. FIND-CKD showed that finerenone slowed eGFR decline in CKD patients without diabetes. ⚠️ Hyperkalaemia monitoring remains mandatory. 👉 Pearl: nsMRA therapy may expand beyond DKD. 8️⃣ CGM is now relevant even in T2D not using insulin. CONNECT RCT showed CGM produced 0.9% greater HbA1c reduction and around 5 hours/day more time-in-range versus routine care. 📲 Clinical message: Seeing glucose can change behaviour, diet, and treatment even without insulin. 9️⃣ Prior PCI without MI is still high residual ASCVD risk. In VESALIUS-CV, evolocumab reduced 3-point MACE, MI, and urgent coronary revascularisation in patients with prior PCI but no previous MI. ❤️ Pearl: “No MI” does not mean “low risk” after PCI. 🔟 Teplizumab is entering real-world T1D disease-modification practice. TEPLI-REAL showed high completion of the 14-day infusion course, with many patients remaining in stage 2 T1D during follow-up. 🧬 Clinical message: T1D screening plus early intervention is becoming actionable. 🎯 Final CME INDIA Take-Home ADA 2026 was dominated by oral incretins, triple agonists, weight-loss pharmacology, CGM beyond insulin, kidney protection beyond diabetes, lipid intensification after PCI, and early type 1 diabetes disease modification.

Published today, the first-ever clinical practice guideline on cardiovascular-kidney-metabolic (CKM) syndrome from the American Heart Association and @ACCinTouch. The focus of this clinical practice guideline is to create a living, working document that provides current knowledge in the field of CKM syndrome aimed at all practicing cardiologists, endocrinologists, nephrologists, and primary care and specialty clinicians who manage these patients. ✍🏼 @ChiadiNdumele @HeartDocSadiya @kardiologykazi @noshreza @virani_md @biykemb @NutritionHF @mandeepbajaj65 @KatherineTuttl8 @RangaswJ @lisaVWMD @KBreathettMD @EmoryFamMed @ShoaClarke @mad_sters @jmortonmd @sripalbangalore @AnumSaeedMD

In today's @TheLancet there are 3 papers on cardiometabolic disease: biology, epidemiology, prevention/treatment. The sobering and all to common story from womb to tomb conveyed in this graphic thelancet.com/journals/lance… thelancet.com/journals/lance… thelancet.com/journals/lance…

A new book by @helenpearson — BEYOND BELIEF— takes us through an 8-decade progression for what is the now considered best medical evidence. Our conversation gets into some incredible historical examples, such as sudden infant death syndrome. In the new Ground Truths. A @NotebookLM infographic on some of the book content below

Just published in JACC @JACCJournals!🫀 Acute HF care is evolving: 📍Rapid diagnosis 📍Early decongestion 📍Timely GDMT initiation 📍Structured follow-up 📍Focus on long-term outcomes, not just symptom relief Grateful to have contributed to this international collaboration & learned so much from the exceptional experts involved in this work. Congratulations to @Jolie_Bruno_ and @AlexMebazaa for the leadership & to all co-authors on this important publication🫀 Read the full paper🔗: doi.org/10.1016/j.jacc.2026.… #HeartFailure #AcuteHeartFailure #JACC @jozinetm @BiykemB @GianluSava @pmyhre

An #ArtificialIntelligence based model for predicting long-term all-cause mortality after acute Myocardial Infarction (the AIMI model) ow.ly/5TU050Z3CQg #EHJDigital #MachineLearning @BruiningNico @rafavidalperez @fwasselbergs @rbcasado

INCLISIRAN ✍️Fast-track lipid-lowering treatment early after an acute coronary syndrome 🌏Real-World-Data on ACS patients ⬇️LDL: 147->30 mg/dl 👍🏻50% achieved goals at 15d 👍🏻100% achieved goals at 30 d doi.org/10.1016/j.athplu.202…

2024 Revision of the level of evidence grading system for ESC clinical practice guideline recommendations II: diagnostic tests and prediction models. Read more in the #EHJ doi.org/10.1093/eurheartj/eh…. #ClinicalGuidelines #EvidenceBasedMedicine @ESCardio @ESC_Journals

From CAD to atherosclerotic coronary artery disease? @TheLancet Commission led by @rallamee includes @DFCapodanno @EuroInterventio Editor-in-Chief , @mirvatalasnag PCRonline Editorial Board member, @NievesGonzalo1 #EuroPCR Course Director, and @nickaram PCR Innovators Day #PCRID Steering Committee Director! #ACC25

👆 Rethinking “Normal” LDL-C: A Physiological Mismatch 📍 LDL receptor kinetics are not aligned with current clinical definitions 📍 Half-maximal receptor-mediated LDL uptake occurs at ~30–40 mg/dL (Km range), far below what we label as “acceptable”. 📍 Binding affinity tells an even harsher story 1️⃣ LDL–LDLR interaction (Kd) suggests significant receptor engagement already at ~10–15 mg/dL. Above these levels, clearance becomes progressively inefficient 2️⃣ Additional LDL is no longer matched by proportional receptor-mediated uptake → plasma accumulation becomes inevitable. 3️⃣ Modern “normal” LDL-C (~100 mg/dL) exists in a biologically saturated system 4️⃣ This is not physiological—it is compensated pathology. Atherosclerosis, then, is not an anomaly 5️⃣ It is the predictable consequence of operating chronically above receptor capacity. 📍 Take-home message We did not adapt physiology to modern LDLc levels We adapted our definitions to a chronically saturated system. doi.org/10.1042/bj3230649 @society_eas @nationallipid

In a randomized study involving 9 general cardiologists & 107 patient cases, assistance from an #LLM led to preferable responses on complex case management vs physicians alone. nature.com/articles/s41591-0…

GLP-1 receptor agonists are increasingly used to treat type 2 diabetes and obesity, and trials have shown reductions in cardiovascular risk and slowing of kidney failure. Adverse events are mostly gastrointestinal. Read the Review Article “GLP-1 Receptor Agonists” by Clifford J. Rosen, MD, and Julie R. Ingelfinger, MD, from @tuftsmedschool and the Maine Medical Center Institute for Research: nejm.org/doi/full/10.1056/NE…

Novel cardiovascular metabolic risk factor mechanisms and therapeutic opportunities: A scientific statement of the ESC Council on Basic Cardiovascular Science, the ESC Working Group on Atherosclerosis and Vascular Biology, the ESC Working Group on Cellular Biology of the Heart, the ESC Working Group on Myocardial Function, and the ESC Working Group on Cardiac Cellular Electrophysiology addressing the complex basis for metabolic disorders and CVD requires a systems-based, multidisciplinary framework spanning cardiology, hepatology, nephrology, endocrinology, metabolism, primary care, and patient-centred perspective #Cardiology #MedTwitter #CardioTwitter #HeartHealth #Healthcare @ESC_Journals @escardio @ehj_ed @CMichaelGibson @EricTopol @DrMarthaGulati @hvanspall @ShelleyZieroth @SubodhVermaMD academic.oup.com/eurheartj/a…

From @JAMA_current: #Obesity is associated with higher risk for 12 #cancer types and accounts for approximately 10% of annual new cancer cases in the US. 📄 This Review summarizes the biological pathways connecting obesity and cancer development. ja.ma/4rkLmTA

Interested in the latest sleep science and getting better quality sleep? New Ground Truths with Prof Yo-El Ju, @WashUNeurology erictopol.substack.com/p/a-m… SRI-sleep regularity index

Obesity and smoking may lead to atrial fibrillation via structural and functional changes in the left atrium. @Adielias5 @gregorymmarcus ahajrnls.org/4rZ2VKk

Lipoprotein(a)-lowering therapies: a promising future. A state-of-the-Art review in #EHJ 👉 ow.ly/V6Rm50YlK3J @RoccoMontone @ehj_ed

Semaglutide and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy (NAION): New 2026 JAMA Ophthalmology Evidence 🔬 Background: Why this study matters Semaglutide, a GLP-1 receptor agonist, is widely used for type 2 diabetes and obesity due to its robust glycemic, cardiovascular, renal, and weight loss benefits. However, emerging post-marketing and observational evidence suggests a possible association with nonarteritic anterior ischemic optic neuropathy (NAION)—a potentially irreversible cause of sudden vision loss. This landmark 2026 nationwide US Veterans cohort study (Heberer K et al, JAMA Ophthalmology, 2026) provides the strongest comparative real-world evidence to date. 📊 Key CME INDIA Clinical Pearls 👁️ Risk Signal: Semaglutide Associated With Higher NAION Risk Semaglutide initiation was associated with a 2.33-fold higher risk of NAION compared with SGLT2 inhibitors. Hazard ratio (HR): 2.33 (95% CI 1.54–3.54; P < 0.001) This represents a statistically robust association in a large real-world cohort. 📉 Absolute Risk Remains Very Low (Reassuring for Clinicians) Absolute incidence was low in both groups: Semaglutide: 0.29% over median 2.1 years SGLT2 inhibitors: 0.13% Absolute excess risk: 0.16 percentage points Incidence rate: Semaglutide: 123 per 100,000 person-years SGLT2i: 67 per 100,000 person-years 📌 Clinical implication: Despite relative risk increase, NAION remains a rare complication. 🧠 NAION: A Devastating but Under-recognized Complication NAION is characterized by: Sudden painless monocular vision loss Optic disc edema Often irreversible visual impairment Associated with vascular risk factors common in diabetes: Diabetes mellitus Hypertension Dyslipidemia Sleep apnea Small crowded optic disc ("disc at risk") ⚖️ Benefit-Risk Balance Still Strongly Favors Semaglutide Semaglutide remains highly beneficial due to: Proven reduction in: Major adverse cardiovascular events (MACE) Heart failure risk Renal disease progression Significant HbA1c reduction (~1–1.5%) Substantial weight loss (~10–15%) 📌 There is no evidence to discontinue semaglutide routinely due to NAION risk. 🧾 Important Clinical Practice Recommendations 👨‍⚕️ Counseling and vigilance recommended—not discontinuation Clinicians should: Inform patients about rare vision complications Educate patients to report immediately if they develop: Sudden vision loss Blurred vision Visual field defects 👁️ High-risk patients who may require closer monitoring: Particularly relevant in patients with: Long-standing diabetes Diabetic retinopathy Optic disc crowding Prior NAION in fellow eye Severe obstructive sleep apnea Multiple vascular risk factors 💊 Drug selection implications in high-risk ophthalmic patients In patients with very high ophthalmic risk, SGLT2 inhibitors may be preferred when appropriate due to: Lower NAION incidence signal in this study Equivalent or superior cardiorenal protection Indian Clinical Context: Highly Relevant India has: High prevalence of diabetes (~101 million adults) Increasing semaglutide use for diabetes and obesity High burden of vascular risk factors and sleep apnea Therefore, early recognition and counseling are essential in Indian diabetes practice. 🧠 Pathophysiological Hypotheses (Not Yet Proven) Possible mechanisms include: GLP-1 mediated vascular autoregulation changes Rapid glycemic improvement causing microvascular perfusion shifts Nocturnal hypotension Optic nerve perfusion vulnerability in susceptible individuals Further mechanistic studies are ongoing. 📌 CME INDIA Bottom Line Message ✅ Semaglutide increases relative risk of NAION (~2-fold) ✅ Absolute risk remains very low (<0.3%) ✅ Cardiometabolic benefits strongly outweigh risks ✅ Do not avoid semaglutide routinely ✅ Counsel patients regarding rare vision symptoms ✅ Consider SGLT2 inhibitors in very high ophthalmic-risk individuals 📚 Reference jamanetwork.com/journals/jam…

Independent of weight loss, semaglutide (Ozempic) improves knee arthritis by cartilage restoration, in both the mouse model and a small randomized clinical trial @Cell_Metabolism cell.com/cell-metabolism/ful…