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    Science

    Sensible Medicine

    Common sense and original thinking in bio-medicine
    A platform for diverse views and debate

    www.sensible-med.com

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    Copyright: © Editors

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    Latest Episodes:
    When to treat (or not treat) a high cholesterol Jan 18, 2026
    Show notes

    I was shocked at the comments on this post.

    Many people, some of them I know to be smart, thought I was nuts for suggesting two middle-aged women who had isolated high LDL-C needn’t take meds because their calculated 10-year risk was less than 3%

    What shocked me is that our guidelines suggest treatment with statins when 10-year risk is ≥ 7.5%. You may not know this but clinicians are supposed to consider cholesterol (and BP) based on overall risk, which include things like age, blood pressure, smoking status as well as HDL. Here is a link to the PCE. It drives me bananas that clinicians don’t go over this with patients. They just look at LDL-c in isolation.

    Content like this comes free of industry support. Please consider becoming a free or paid subscriber.

    Experts chose this a 7.5% threshold because they felt it was the point where the absolute risk reduction from statins (about 20-25% relative risk reduction) for nonfatal cardiac events outweighed any potential downsides of statins. It is an arbitrary threshold.

    The thinking: We know from many RCTs that statins reduce future risk by about 20-25% over 5 years. So .25 x the estimated risk outputs the absolute risk reduction. Let’s say a person has a calculated risk of 10%. They can expect a 2.5% risk reduction (.25 x 10% = 2.5%) over 10 years. But .25 x 3% = .75, so a person with an estimated risk of 3% who takes a daily pill for 10 years goes to 2.25%. That’s not much.

    Here are some pics of the pushback I recieved:

    My colleagues rightly point out that atherosclerosis of the coronary arteries is a slow process and longer exposure to lower LDL-c is beneficial. They feel that the 10-year horizon is too short. They cite something called Mendelian randomization studies which find that people who were born with genetic profiles that cause low cholesterol also have low rates of heart attacks.

    I wrote a post about this. I actually think that statins and blood pressure drugs may have greater effects in younger people who are at lower risk.

    But come on. Both individuals who I helped calculate risk were below 3%. That’s too low to worry about.

    Further, if you think we treat people with elevated LDL levels who have this low of a risk, why do we need risk calculators? Or…why don’t we just treat everyone above a certain age, since age is the largest driver in the calculators?

    These are issues I spoke with Drs Foy and Murthy about. I learned a ton. I hope you will too.

    Topics include:

    * The value of risk calculators

    * The uncertainty of prediction

    * The best time window to consider (statin trials were for 5 years; can we assume effect sizes over 5 years are similar at 30 years?)

    * The causal role of LDL-c vs “metabolic health”

    * The value of coronary artery calcium testing

    * Lipoprotein (a)

    Academic people like to make fun of podcasts, but I can’t imagine a more educational 40 minutes. Andrew and Venk are two of the most thoughtful people in cardiology today.

    Enjoy and consider supporting Sensible Medicine


    This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

    This Fortnight in Medicine XVII Jan 14, 2026
    Show notes

    Medical Management and Revascularization for Asymptomatic Carotid Stenosis

    Vagus nerve-mediated neuroimmune modulation for rheumatoid arthritis: a pivotal randomized controlled trial

    We spent quite a bit of time talking about blinding. This is the table on the adequacy of blinding from the supplement. It does seem like blinding was less than perfect.


    This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

    This Fortnight in Medicine XVI Dec 31, 2025
    Show notes

    We try to answer the remainder of your AUA questions. We will be back in the new year with more article discussions!

    Here are a few of the things we referenced.

    GDMT Bugs Me: A bit of a rant against the standard of care

    A Plan to Refocus Primary Care

    Sacrificing patient care for prevention: distortion of the role of general practice

    The Great Colonoscopy Debate

    Arthroscopic Partial Meniscectomy versus Sham Surgery for a Degenerative Meniscal Tear


    This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

    This Fortnight in Medicine XV Dec 17, 2025
    Show notes

    We cover questions from Amy J, Benjamin Hourani, Diana Stiles Friou, Chris Costas, Errol Laurie, Jim Healthy, Elizabeth Fama, Never Dull, Rod Rodriguez, Ellison Burns, David Araujo, and George.

    We have more to come!

    One nice reference I found while looking into some of the topics:

    DMSO Is Not a Cure-All. But the FDA’s Panic Over It Birthed a Myth


    This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

    This Fortnight in Medicine XIV Dec 03, 2025
    Show notes

    Vascular and inflammatory diseases after COVID-19 infection and vaccination in children and young people in England: a retrospective, population-based cohort study using linked electronic health records

    Comparison of an Initial Risk-Based Testing Strategy vs Usual Testing in Stable Symptomatic Patients With Suspected Coronary Artery Disease: The PRECISE Randomized Clinical Trial


    This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

    This Fortnight in Medicine XIII Nov 19, 2025
    Show notes

    European Study of Prostate Cancer Screening — 23-Year Follow-up

    Association Between Baseline Diastolic Blood Pressure and the Efficacy of Intensive vs Standard Blood Pressure–Lowering Therapy

    Further Reading

    * Effects of intensive blood-pressure control in type 2 diabetes mellitus

    * A Randomized Trial of Intensive versus Standard Blood-Pressure Control

    Sensible Medicine is 100% reader-supported. If you appreciate our work, consider becoming a free or paid subscriber.


    This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

    This Fortnight in Medicine XII Nov 05, 2025
    Show notes

    Effects of Intensive Blood Pressure Control in Patients With Frailty: A Post Hoc Analysis From ESPRIT

    * Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label, blinded-outcome, randomised trial

    * Reduction of Antihypertensive Treatment in Nursing Home Residents

    Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults

    * A trial to evaluate the safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine in populations of adults ≥65 years of age with different prior pneumococcal vaccination


    This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

    This Fortnight in Medicine XI Oct 22, 2025
    Show notes

    Total cholesterol and all-cause mortality by sex and age: a prospective cohort study among 12.8 million adults

    * The Ideal Cholesterol Level ... Depends...And Cannot Be Determined From Observational Studies

    Structured vs Self-Guided Multidomain Lifestyle Interventions for Global Cognitive Function: The US POINTER Randomized Clinical Trial

    * Can We Please Stop Asking if Crossword Puzzles Prevent Dementia?


    This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

    This Fortnight in Medicine X Oct 08, 2025
    Show notes

    Two papers this week, with a bunch of articles that we referenced in the conversation. Also, the last Fortnight podcast was accidentally posted behind a paywall. It is now up and free to listen to. My apologies.

    Sensible Medicine is reader-supported. If you appreciate our work, consider becoming a free or paid subscriber.

    Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial

    * Folate Receptor Alpha Autoantibodies in Autism Spectrum Disorders: Diagnosis, Treatment and Prevention

    * Association Between Maternal Use of Folic Acid Supplements and Risk of Autism Spectrum Disorders in Children

    * Cerebral folate receptor autoantibodies in autism spectrum disorder

    * What Is Leucovorin, the Medicine Being Approved for Autism Treatment?

    * Clinicaltrial.gov search

    Effects of Glucagon-Like Peptide 1 Receptor Agonist Initiation in Patients With Heart Failure With Reduced Ejection Fraction and Implantable Cardiac Devices

    * Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes

    * Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes

    * Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction

    * Increased Risk of Heart Failure Hospitalization With GLP-1 Receptor Agonists in Patients With Reduced Ejection Fraction: A Meta-Analysis of the EXSCEL and FIGHT Trials


    This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

    This Fortnight in Medicine IX Sep 24, 2025
    Show notes

    We go all observational this week. A look at data suggesting the safety of GLP-1s and a re-examination of data on patient/doctor race concordance/discordance (a topic Adam said we should not study, and then John forces him to).

    GLP-1 Receptor Agonists and Cancer Risk in Adults With Obesity

    Physician–patient racial concordance and newborn mortality

    Original, 2020 article: Physician–patient racial concordance and disparities in birthing mortality for newborns


    This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

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