Researchers trace drugs and diseases from DNA drifting through city air
DNA is in the air, and scientists are finally learning how to read it.
In Dublin — a city known for its cozy pubs, flowing Guinness, and music that spills into cobbled streets — researchers have discovered something far less visible drifting through the air: traces of cannabis, poppy, and even psychedelic mushrooms.
Not the plants themselves, but their DNA.
A groundbreaking study by scientists at the University of Florida reveals that environmental DNA, or eDNA, vacuumed straight from the air, can offer stunning insights into the world around us. These range from identifying endangered wildlife and tracking human pathogens to detecting allergens and illicit drugs.
'The level of information that's available in environmental DNA is such that we're only starting to consider what the potential applications can be, from humans, to wildlife to other species that have implications for human health,' said David Duffy, Ph.D., lead author of the study and professor of wildlife disease genomics.
Originally designed to study sea turtles, the technique developed by Duffy and his team has since transformed into a powerful tool for decoding the biological fingerprints of nearly any environment, including air, oceans, or forests.
And all it takes is an air filter and a day in the lab to detect signs of nearly every living thing that's grown, passed through, or shed cells nearby.
'When we started, it seemed like it would be hard to get intact large fragments of DNA from the air. But that's not the case. We're actually finding a lot of informative DNA,' Duffy said in a release.
'That means you can study species without directly having to disturb them, without ever having to see them. It opens up huge possibilities to study all the species in an area simultaneously, from microbes and viruses all the way up to vertebrates like bobcats and humans, and everything in between.'
In Dublin, researchers found DNA signatures from hundreds of sources, including human pathogens, bacteria, and allergens like peanut residue and pollen.
In another striking demonstration of eDNA's potential, the researchers were able to trace the origins of bobcats and spiders by analyzing DNA captured from the air in a Florida forest.
This powerful analysis also came with remarkable speed and efficiency. The team showed that a single researcher could process DNA from every species in a given area in just a day, using compact, low-cost equipment and cloud-based software. When trying to save and conserve wildlife, knowing where an animal originates from can be as important as knowing where it currently is.
'It seems like science fiction, but it's becoming science fact,' Duffy said. 'The technology is finally matching the scale of environmental problems.'
The researchers say the implications of the study are vast. The method could help track disease outbreaks, identify endangered species, and even detect drug activity, all silently captured by the breeze.
However, the same tools can also reveal sensitive human genetic information. The researchers have called for ethical guidelines to keep pace with the fast-moving science of eDNA.The study has been published in Nature, Ecology and Evolution.
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Associated Press
an hour ago
- Associated Press
Sire Search Identifies Top 5 Platforms to Boost Biotech Career Growth
Hey, biotech folks! Whether you're a lab whiz itching to land your next role in drug discovery or a hiring manager hunting for the perfect candidate to boost your startup, the life sciences world is buzzing with potential. But, real talk—finding the right job or talent in this fast-moving industry can feel like trying to spot a single cell under a microscope. Overwhelming, right? That's were specialized recruitment websites swoop in like career superheroes. I've rounded up the five best platforms to help you navigate the biotech job maze, and guess what? SIRE Searchis leading the charge with its sharp, tailored approach. Let's dive in and see why these sites are your new allies for crushing it in biotech! 1. – Your Career's Guide A recruitment platform that feels like it knows you better than your lab partner. That's SIRE Searchin a nutshell. Based in Haarlem, Netherlands—a charming spot, by the way—SIRE has been shaking up the life sciences scene since 2012. Whether you're into pharmaceuticals, medical devices, or even fast-moving consumer goods (yep, they've got that covered), SIRE's the place to find your next career win. Their reverse recruitment approach is like a secret weapon. Instead of tossing a pile of job listings your way, they do the heavy lifting first. Using data and market insights, their team—packed with recruiters who actually get biotech—handpicks roles that match your skills and goals. One Trustpilot reviewer raved, 'SIRE landed me a job that's spot-on for my expertise. They were quick and genuinely cared!' With a 4-star rating, they're clearly hitting the mark. 2. – The U.S. Biotech Hub Let's zip over to the States for BioSpace, a heavyweight for biotech and pharma jobs. With over 4,000 active listings, this sites like a treasure chest for anyone looking to dive into or climb higher in the U.S. biotech scene. From lab techs to execs, BioSpace has roles for every step of your journey. What's the deal with BioSpace? It's more than a job board—it's a whole community. You can narrow down searches by niche (like gene therapy or clinical trials) or location, so you're not stuck scrolling through irrelevant posts. They also dish out extras like industry updates, career tips, and their 'Best Places to Work' report, which is like a VIP list for biotech companies. The downside? It's mostly U.S.-focused, so it doesn't have SIRE's global reach. But for North American job seekers, BioSpace is a goldmine. 3. – Your Global Career Connector Dreaming of a biotech career that takes you worldwide? Meet Preclinical. With offices in places like the UK, Singapore, and the U.S., this platform hooks up candidates with roles in everything from drug development to regulatory affairs. It's like having a friend who knows the hottest jobs on every continent. Proclinical's strength is precision. Their recruiters dig into what employers need—skills, culture, the whole package—and match that with a huge candidate network. It's like they're playing career matchmaker, and they're good at it. They don't have SIRE's data-driven reverse recruitment trick, but their global scope is a big win for anyone wanting to think beyond borders. Plus, their blog's full of practical tips, like how to tweak your CV or nail an interview, which is super handy. 4. – The Science Lover's Hangout Next up is New Scientist Jobs, the friendly, all-purpose spot for science buffs. It covers a range of fields, but its biotech section is packed with roles in areas like vaccine research or molecular biology. Whether you're in Europe, the U.S., or elsewhere, this platform's global vibe makes it a welcoming place to explore. Why's it worth your time? It's easy to navigate, with filters to zero in on jobs by expertise or location. Their blog's a gem, too, with career advice and industry scoops that keep you in the loop. It's not as biotech-focused as SIRE, so you might need to sift a bit to find the right role. But if you're curious and love poking around, New Scientist Jobs is a solid bet. 5. – The Job-Finding Shortcut Last up is BioPharmGuy, the quirky underdog we're rooting for. Instead of hosting job listings, it points you straight to biotech company career pages, helping you dodge crowded job boards and find hidden opportunities. It's like a map of buried treasure. You can search by region or niche—like cell therapy or diagnostics—which makes it easy to target your sweet spot. The catch? It's more of a DIY experience, so you won't get the hands-on support you'd find with SIRE's recruiters. But for those who enjoy a bit of career sleuthing, BioPharmGuy is a clever tool to stand out. Why SIRE Search Takes the Crown? Let's give a shoutout to SIRE Searchfor stealing the show. Their reverse recruitment strategy is like having a career coach who's always one step ahead. By tapping into data and market trends, they find roles that fit you like a perfectly calibrated pipette. Their recruiters are biotech enthusiasts who speak your language and genuinely care about your next step. SIRE's focus on Europe—where biotech is thriving—gives them the edge, with connections to everyone from tiny startups to massive corporations. One candidate on Trustpilot said, 'SIRE made my job search feel effortless. They found me a role that's exactly where I want to be.' Employers love them, too, thanks to their knack for delivering candidates who nail both the skills and the vibe. Whether you're after a temp role or a corner office, SIRE's your partner in crime. 5 Tips to Nail Your Biotech Job Hunt Ready to hit these websites and land your dream role? Here's how to make it happen: Let's Wrap It Up The biotech world is full of possibilities, and these websites are your key to unlocking them. SIRE Searchleads the pack with its smart, personalized approach and deep love for life sciences. BioSpace, Preclinical, New Scientist Jobs, and BioPharmGuy are also stellar, each bringing their spark to the table. So, spruce up that resume, dive into these platforms, and get ready to make waves in biotech. Your next big opportunity is out there—grab it! Media Contact Company Name: Sire Search Email: Send Email Address:Staten Bolwerk City: 12011 MK Haarlem Country: Netherlands Website: Press Release Distributed by To view the original version on ABNewswire visit: Sire Search Identifies Top 5 Platforms to Boost Biotech Career Growth
Medscape
8 hours ago
- Medscape
Sibeprenlimab Halves uPCR in IgA Nephropathy Trial
VIENNA — Sibeprenlimab, a novel selective immune antibody, reduced the urine protein-to-creatinine ratio (uPCR) by more than half in patients with immunoglobulin A (IgA) nephropathy, according to an interim analysis of the VISIONARY trial. Beyond this clinical effect, a notable observation was the lack of safety concerns, especially given that, although sibeprenlimab is a selective agent, there may have been unexpected off-target effects. 'Safety's been a key consideration with these drugs,' study presenter Vlado Perkovic, MD, PhD, provost and scientia professor, University of New South Wales, Sydney, Australia, told Medscape Medical News . Sibeprenlimab represents a new mechanism of action and 'we don't yet fully understand the profile, so we've been looking at that data very carefully,' explained Perkovic. 'In particular, the infection risk has been my biggest concern, given we know that infections are dramatically increased in people with steroid therapy for example, in IgA nephropathy.' The results of the trial — the largest to date in the field — were presented at the 62nd European Renal Association Congress 2025 on June 6 and drew a warm applause from the audience. An Underestimated Condition IgA nephropathy is estimated to affect 2.5 per 100,000 people per year, although 'it's possible that that number is a significant underestimate,' said Perkovic. Diagnosis typically occurs between 20 and 40 years of age. And, despite supportive care, the majority of patients have a high lifetime risk of end-stage kidney disease (ESKD), with up to 50% of patients progressing to ESKD within 20 years of their clinical presentation. 'It's quite likely we've underestimated just how important this condition is,' said Perkovic, but 'we're fortunate that we're in the middle of something of a golden age of developing new treatments.' A number of therapies have been shown to reduce the risks associated with the disease, although they do not necessarily address the immunological basis of the condition. In addition to newer treatments, 'corticosteroids have long been used for people with IgA nephropathy,' Perkovic said, 'but of course, corticosteroids also have a range of different effects across the immune system,' which can lead to adverse outcomes. Sibeprenlimab is a selective IgG2 antibody that binds to and inhibits the biological activity of APRIL (a proliferation-inducing ligand), which is produced by mucosal epithelial and myeloid cells and binds to B cells. APRIL regulates B-cell-mediated immune responses and mediates IgG and IgA class switching in mature B cells. It is these two actions that make APRIL a key factor in the so-called 4-Hit process in the pathogenesis of IgA nephropathy, which results in the deposition of immune complexes in the glomerulus, leading to proteinuria and loss of kidney function. Phase 3 VISIONARY TRIAL Following on from the successful phase 2 ENVISION trial of sibeprenlimab, the researchers undertook the phase 3 VISIONARY trial, an ongoing study involving patients with biopsy-confirmed IgA nephropathy from 240 sites in 31 countries, who were randomized to sibeprenlimab or placebo for 100 weeks and followed up for a further 12 weeks. All patients were required to have a uPCR of ≥ 0.75 g/g or urine protein excretion of ≥ 1.0 g/day, an estimated glomerular filtration rate (eGFR) of ≥ 30 mL/min/1.73 m2, and to have been on a stable dose of either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, with or without a SGLT2 inhibitor, for ≥ 3 months prior to screening. For the current pre-specified interim analysis, Perkovic reported the efficacy and safety results in the first 320 randomized patients (152 in the sibeprenlimab group and 168 in the placebo group), focusing on the primary endpoint of 24-hour uPCR at 9 months vs baseline, with eGFR and other data expected to be presented in 2026. The median age of the patients was 42-43 years. There were proportionally fewer females in the sibeprenlimab group (34.2%) vs the placebo group (40.5%). The majority of the patients were Asian, at 61.8% and 56.5%, respectively. Compared with a rise in uPCR at the 9-month follow-up in the placebo group, sibeprenlimab was associated with a 50.2% reduction in uPCR, giving a highly significant placebo-adjusted treatment effect of 51.2% ( P < .0001). Importantly, the benefit of sibeprenlimab on uPCR was seen as early as 4 weeks after initiating treatment and continued to accrue throughout follow-up. Ronald T. Gansevoort, MD, PhD, professor of medicine and a nephrologist at the Department of Nephrology, University Medical Center Groningen, Netherlands, who co-chaired the session, told Medscape Medical News that the results look 'very promising.' 'Recently, we have had several agents working in different ways that all show proteinuria lowering,' he continued, but the results from those studies show that the improvements seen in VISIONARY are 'the best proteinuria lowering' seen so far. Gansevoort noted, however, that this remains an interim analysis, and that he is really looking forward to seeing the kidney function results, adding: 'It was a little bit of a pity that they were not allowed to show at least the 9-month interim data on kidney function, which would have been so interesting.' Safety Results In terms of safety, the proportion of patients experiencing a treatment-related treatment-emergent adverse event (TEAE) was marginally lower with sibeprenlimab, at 32.9% vs 31.0% with placebo. The proportion of patients having a TEAE that led to treatment discontinuation was 0.7% vs 2.4%, respectively, and there were fewer severe and serious TEAEs with the experimental drug. 'If we focus on the infection-related adverse events,' Perkovic said, 'we can see that rates were numerically slightly higher in the sibeprenlimab than the placebo group, with a pattern that was broadly consistent, but with perhaps a slight excess of COVID 19.' He noted that this was 'the reverse of the pattern we've seen in the phase 2 trials, suggesting a chance' outcome. 'The data so far look remarkably encouraging,' he added. There's really no suggestion of an increased risk of infection,' with no opportunistic infections identified, 'and certainly no deaths.' More data is required from the ongoing follow-up to support what has been observed so far, but if the final results do bear out both the efficacy and safety outcome, it will show that sibeprenlimab is 'a precision approach to the fundamental abnormality in IgA nephropathy: that's the really exciting part,' said Perkovic. The study was funded by Otsuka Pharmaceutical Development and Commercialization. Perkovic declares relationships with Amgen, AstraZeneca, Bayer, Biogen, Boehringer Ingelheim, Chinook Therapeutics, Eli Lilly & Company, Gilead Sciences, GlaxoSmithKline, Guard Therapeutics, Incyte, Janssen, Merck, Mitsubishi Tanabe Pharma, Mundipharma, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Sanofi, Shaanxi Micot Technology, Travere Therapeutics.
Medscape
9 hours ago
- Medscape
Jun 06 2025 This Week in Cardiology
Please note that the text below is not a full transcript and has not been copyedited. For more insight and commentary on these stories, subscribe to the This Week in Cardiology podcast , download the Medscape app or subscribe on Apple Podcasts, Spotify, or your preferred podcast provider. This podcast is intended for healthcare professionals only. In This Week's Podcast For the week ending June 6, 2025, John Mandrola, MD, comments on the following topics: Listener feedback on cardiac sarcoidosis, out-of-hospital cardiac arrest, less is more when it comes to post-stent antiplatelets, lipoprotein(a), and atrial fibrillation in HFpEF. Dr Riina Kandolin from Helsinki, Finland, writes via email that I should clarify some of my comments on the cardiac sarcoidosis (CS) paper I made last week. The paper I spoke about last week from a primarily Dutch and Minnesota group compared societal recommendations for an ICD vs cardiovascular magnetic resonance imaging (CMR) phenotyping in patients with suspected CS. The key word was 'suspected' CS. In that study, in the European Heart Journal , CMR phenotyping by (1) no late gadolinium enhancement (LGE) and normal EF, (2) no LGE and abnormal EF, (3) pathology-frequent LGE, and (4) pathology-rare LGE, performed better than professional society recommendations for ventricular tachycardia (VT). Dr Kandolin pointed me to an incredible Circulation EP paper from their group in Helsinki on 305 patients with either biopsy-proven CS (just under half) or highly suggestive by criteria. Right away, this is a different population because the first study looked at patients with distant sarcoidosis (say the lungs) and were evaluating for cardiac sarcoidosis while the second study, in Circulation EP this year, studied patients with proven CS. Two main points of difference arise. In patients with true CS, all have pathology-frequent LGE. So it does not distinguish risk. Rather, the Finnish group showed that it was the degree (and somewhat the distribution) of LGE that predicts sudden death and VT. They found that myocardial LGE making up >9.9% of left ventricular (LV) mass or affecting >6 LV segments may suggest prognostically significant LV involvement and a high risk of sudden cardiac death (SCD). This analysis and its implications bear similarities to what we do for hypertrophic cardiomyopathy (HCM). Namely, in HCM, there is a risk score that corresponds to a yearly risk of VT. If th 5-year threshold reaches >6% for sudden cardiac death, then an ICD is recommended. ESC recommends a similar risk score prediction for laminopathies as well. ICDs for criteria above a risk threshold. The Finnish authors therefore suggest in their discussion that their CMR findings could have clinical relevance. Quote: In patients who have no other guideline-based class I or IIa indications, implantation could be considered if LGE mass is >9.9% by the full-width at half-maximum method or the LGE involves >6 LV segments. Less extensive LGE predicted a 5-year SCD/VT rate <7% with an SCD risk of 0.6 per 100 patient-years, and in these patients other EP studies or close surveillance with repeated risk assessments could be discussed at shared decision-making . If you care about CS and risk stratification, this is an excellent paper. It's worthy of a bookmark. I appreciate the feedback because I learned a lot. My one comment — and this is not at all a criticism of the paper (or papers) — but as a doctor I struggle with these risk thresholds. Say in HCM, what if the 5 year-risk is 5% not 6%. Or in this case of CS, the LGE mass is 7% not 9.9%? The dichotomization of implantable cardioverter-defibrillator (ICD) or no ICD of continuous variables makes me nervous when the outcome is surviving sudden death because you have an ICD. I realize it would be unwise to place ICDs in all patients, including low-risk people, because of ICD harm, but not having an ICD is also a risk. I don't know the answer and perhaps there never will be an answer to finding the ideal patient for an ICD, but HCM and CS are clearly different from RCT-based heart failure (HF) criteria. In HF, we have entry criteria from trials — albeit old trials. Sort of. We used to be able to say that if you are like a MADIT-2 patient, you have a 30% lower mortality with an ICD compared to no ICD. The modern problem is that medical therapy is a lot better, and that 30% benefit may be a lot less. By the way — that is why if you practice in Europe, you should be participating in PROFID EHRA trial of ICD vs no ICD in ICM. One practical comment from my experience is that if a CS patient has heart block and you are implanting hardware, it seems wise to strongly consider an ICD if the LGE is even close to the threshold. The listener feedback is great. I learn a ton from it. Thank you. The American Heart Association sent me two emails yesterday regarding their efforts to increase awareness of bystander CPR. One was a National Football League player named Justin Reid who is leading an effort; the other email said the Atlanta Falcons are teaming up with the AHA to equip players and coaches with the lifesaving CPR (cardiopulmonary) skills during National CPR and AED (automated external defibrillator) Week. The second note is that Circulation: Outcomes published a paper today from a group at Mid-America finding that resuscitation practices for out-of-hospital cardiac arrest (OHCA) differ by geographies. Namely, compared to White catchment areas, communities serving Black and Hispanic have lower rates of OHCA survival. Of course, the causes could be a lot of things, but the research team noted that in Black/Hispanic areas, first responders were less likely to recognize cardiac arrest, police were less likely to respond to a cardiac arrest, and patients were less likely to be defibrillated. Basically, community-level quality of OHCA was less than what it is White catchment areas. And this may explain the differences in survival. I think it explains some of the differences. But OHCA survival rates are complicated, and differences could also be due to severity of disease. My point in highlighting OHCA is that it's one of the highest value interventions in all of medicine. I have spent many hours on this podcast discussing new treatments with marginal benefit. Bystander CPR and an adequate EMS system is hugely valuable. Why? Because only 10% of patients with OHCA in the US survive. Ventricular fibrillation (VF) without CPR or an automated external defibrillator (AED) occurring out of the hospital is nearly 100% deadly. A VF patient depends on the knowledge and availability of his or her neighbors. Since survival is so bad, any tick up is likely highly cost effective. Bystander CPR and public AEDs are nearly free of risk — it's all benefit. I know OHCA care isn't as exciting as the newest ablation catheter, or stent, or new drug, but it's surely a lot higher in value than either of these things. A new tricuspid valve clip or more AEDs in your city? I'd go with the latter every time. So good on the AHA — and the NFL. The other thing I love about promoting OHCA is that it brings communities together for an obviously great and totally uncontroversial cause. Is a Year of Dual Antiplatelet Therapy Magical Thinking? I hesitate to delve into this topic because it is perhaps the most confusing in all of cardiology. But I will, because yet another study finds that 'less is more.' This seems too simple to state, but the idea is that having a metal cage propping open a coronary lesion is neither a fix nor is it free. Metal in the coronary attracts platelets and then clots can form. Stent thrombosis is a medicalized jargon, but it's a terrible outcome because you go from 0% blockage to 100% blockage. The good news is that the body eventually (and usually) forms a layer around the stent protecting it from the circulating platelets. This we call, and, jargon-wise it is a whopper, endothelialization. The problem of course is that antiplatelet drugs are also not free — blocking platelets increases the risk of major bleeding in the gut, kidneys, and brain. So, the quest — and it is a quest — is to find the Goldilocks recipe for preventing thrombotic or clotting events (such as myocardial infarction) with the lowest rate of bleeding. The usual regimen is to use two antiplatelet drugs (aspirin and either clopidogrel or ticagrelor or prasugrel) for a period before switching to single antiplatelet. Perhaps you can see the complexity already. There are four antiplatelet drugs of varying intensity; and there are near-infinite ways to break up time after the stent, and different types of patients. There's acute coronary syndrome (ACS) vs stable coronary artery disease (CAD) patients; there's high-bleeding risk and not-high-bleeding risk patients; and then there are different stents. You start multiplying and you get about a quadrillion different ways to do antiplatelet drugs. Today I will tell you about one recent trial — but know that there are many. The South Korean trial was called 4D-ACS. It was a comparison of two prasugrel-based strategies in about 650 patients who had PCI and stent during an ACS: one group gets one-month of dual antiplatelet therapy (DAPT) (aspirin 100 mg + prasugrel 10 mg, except the prasugrel dose is adjusted to 5 mg for age>75 or body weight < 60 kg vs the control arm: 12 month of DAPT with aspiring 100 mg and prasugrel 5 mg. The primary endpoint is called NACE. Not MACE , but NACE — or net adverse clinical events: death, myocardial infarction (MI), stroke, ischemia-driven revascularization and bleeding. Bleeding also has 5 different grades. This trial measured types 2-5, so minor bleeding was not included. The results: NACE occurred in 4.9% of the 1-month DAPT group and 8.8% of the 12-month DAPT group. The trial was a non-inferiority comparison. This is a good use of non-inferiority. Why? Because the short duration is very much less intense than the standard 12-month DAPT regimen. If it was just as good, it would be a win. Indeed the 4.9% vs 8.8% easily made non-inferiority and in fact with a hazard ratio [HR] of 0.51; 95% CI: 0.27-0.95; P = .034), it also made superiority. The driver of the lower NACE was a 77% lower rate of bleeding in the short duration DAPT arm: 1.2% vs 5.5%. There were almost no differences in thrombotic events such as MI, stroke, ischemia-driven revascularization. I cover this study because it is such a clear result. If using prasugrel, a one-month DAPT regimen is surely better than 12-month DAPT. You would think it's clear now, but it is surely not. First of all, all patients were Korean, and Asians may respond differently to antiplatelets. Second, the study used a type of stent that is not used in the US. Third, what about 1-month DAPT vs 3 months? What about combos of different antiplatelets. Like aspirin/clopidogrel vs clopidogrel. In general, the trend of late is for shorter courses of DAPT. But my solution in real life is to use one of the most important tools in all of medicine: phone-a-friend. I call my interventional cardiology colleague and ask what they think. They've done the stent and a bifurcation stent in the proximal LAD is going to be different from a mid-circumflex lesion. Perhaps I can make these general statements: ACS patients generally require longer DAPT duration (12 months) due to higher thrombotic risk Non-ACS patients most likely can safely use shorter DAPT durations (6 months for DES. Patients with high bleeding risk may benefit from abbreviated DAPT (1-3 months) regardless of presentation P2Y12 monotherapy after initial DAPT period shows promise for reducing bleeding while maintaining efficacy An individual risk assessment may prove helpful in guiding duration and intensity of DAPT. Final comment: if you are having an ST-elevation myocardial infarction (STEMI), you want a stent done fast. If you have chronic CAD, medical therapy first avoids the entire issue of deciding on the combination of antiplatelets. Sadly, this doesn't happen often enough in many places in the US. JAMA Cardiology has published an interesting study looking at the value (or lack of value) in adding Lp(a) into the new PREVENT equation. The first thing to say is that I covered the AHA's PREVENT equation in August of last year. Proponents of PREVENT say it's better than the standard PCE — which outputs 10-year risk of atherosclerotic events. Of course, the proponents of PREVENT don't just say it's better. PREVENT has been validated in observational datasets. PREVENT differs from the pooled cohort equation because it incorporates kidney function, statin use, social determinants of health and removes the race category. It also starts at a younger age. The most provocative aspect of PREVENT is that it simultaneously is felt to be more accurate, but it lowers estimates of CV risk and lowers the number of statin-eligible people. Gulp. Double gulp. Anyways, the question of the JAMA Cardiology study was whether the PREVENT equation can be made better by adding Lp(a) — which as you probably know is mostly genetically determined and, when elevated, is strongly associated with higher risk of CV events. Since race is removed from PREVENT and race can bear on Lp(a), adding it could be very important. Here is that they did. Two databases — UK biobank and MESA. This was big, big data. Both databases have long-term follow-up. Individuals in the database were put into 4 categories: low risk (5%), borderline (5%-7.5%), intermediate (7.5%-20%), and high risk (> 20%) Then they measured 10-year event rates and correlated it with Lp(a) levels overall and by risk category. Of course they do adjustments for age and sex. The main endpoint is the net reclassification improvement or NRI, which is complicated. Let me try to explain: NRI measures how well a new risk prediction model reclassifies people compared to an old model, but it does this by tracking movements in both directions and netting them out. The NRI splits reclassification into events (people who actually had the outcome) and non-events (people who didn't). For each group, it calculates: Proportion who moved up in risk categories minus the proportion who moved down This gives you a net movement figure for each group. The problem comes in relative vs absolute differences. You see this in the NRI studies of coronary artery calcium (CAC) where, when you consider absolute numbers, more people don't have events and are actually misclassified using NRI. I asked the AI tool Claude about this — because Claude helps — and Claude calls this 'The Conceptual Trap,' and I think it's worth talking about. Claude says that people often interpret NRI as "20% improvement in classification" when it's really "20% net improvement after accounting for movements in both directions." The absolute amount of reclassification — which tells you how much the models actually disagree — gets hidden in this netting process. In this study, they measured NRI both categorically — that is, how many moved into a different risk category based on Lp(a) (ie, going from borderline risk to intermediate risk) — and they also measured the NRI category-free (which is simply whether the patient moved up or down in risk at all). They differed — a lot. The category-free NRI for atherosclerotic events using Lp(a) was about .06 (or 6%). Now, the categorical NRI was 10 times lower — at 0.6% The way I would try to translate that is to say that adding Lp(a) reclassifies about 6% of people on a net basis for CV risk, but it is far less valuable for moving people between low, borderline, intermediate and high-risk categories. Here it was less than 1%. Now, the study did something else that is perhaps somewhat useful. They looked at subgroups of people who may get more reclassification. They found that adding Lp(a) resulted in slightly more reclassification for borderline risk and low risk people. But I have to say the differences are quite modest. For instance, the NRI for low-risk CHD prediction was 10% vs 7.5% for intermediate risk. 10% vs 7.5% — it doesn't seem like a big difference. This is a nice effort. Adding Lp(a) helps a little with prediction. A low-risk person who has an Lp(a) may want to take statins. A borderline person with a low Lp(a) may pass. But here's the thing, and I feel it's the same with CAC. I've seen patients for nearly 30 years in middle America, and the vast majority, perhaps 90% of people cannot conceptualize the difference between 7% and 9% vs 13% risk of 10-year events. I've had lipids done recently and I am borderline risk. And I can't really conceptualize 10-year risk of a nonfatal event. Maybe you can. Two reasons I struggle. One is that philosophically, I think much of disease and health is good and bad luck. As in…stuff happens. The second reason I struggle with 10-year risk prediction is relative to Ukraine attacking Russia's planes and the threat of World War III: how much worry should I place in whether my nonfatal CV risk is 7% without Lp(a) vs 9% with Lp(a)? I come back to my bottom-line when it comes to prevention: there are maximizers who want to do everything. For them, Lp(a) seems useless because they are already on aggressive lipid lowering. There are minimizers who aren't taking pills regardless. And for these patients, Lp(a) is also useless. So, for the few who sweat the details, fine — add Lp(a) to the mix. Publishing in EuroPace , a group of prominent researchers re-analyzed the TOPCAT Americas trial looking at the role of AF in predicting bad outcomes in patients with heart failure with preserved ejection fraction (HFpEF). Recall that TOPCAT is one of the most important trials in cardiology. Sadly, it was marred by data irregularities from Russia and Georgia. TOPCAT was spironolactone vs placebo in HFpEF. The hazard ratio (HR) was 0.89 for the composite primary of death, cardiac arrest, or heart failure hospitalization (HHF). The 11% reduction did not reach statistical significance. But all-cause death was 22% in the Americas and only 8% in Russia/Georgia, and the drug had little effect in that region. Further metabolic studies found that a third of patients supposedly randomized to spironolactone had undetectable metabolites. Excluding Russia and Georgia, TOPCAT was positive with a HR of 0.82 and a confidence interval of 0.69-0.98. I think this is a really important point. Ok, now to the EuroPace paper. The problem with studying HFpEF is it is diverse condition — unlike HFrEF. The authors, mostly EP docs, were interested in AF effects in HFpEF. Specifically, whether AF is simply a marker for advanced CV disease or is it an independent risk factor. They made two groups: Study patients who had AF before or at study entry. This was the 'any AF' group. Study patients with ongoing AF who had it at entry. Then they propensity-matched patients with no AF and looked at outcomes. I know, it's pretty easy to predict what will happen. Before I tell you the results, I hope you are thinking: small, hyperdynamic, noncompliant left ventricles are not going to do well with losing the atrial kick when AF occurs. The primary outcome of these comparisons was CV mortality. About 580 patients in TOPCAT who had any AF and 400 had ongoing AF. And they found that: Any AF was associated with a statistically significant increase in CV hospitalization, HHF, and progression of HF. Any AF, however, was not associated with an increased risk of sudden death. Ongoing AF was associated significantly with CVD, pump failure death, CV hospitalizations, and HHF. It was interesting to me that neither any AF or ongoing AF was not strongly associated with sudden death. AF seemed to associate mostly with progression of HF or pump failure. This paper has a lot of complicated comparisons, but I think it can be summarized as AF is a bad thing to have with underlying HFpEF. The question of course, the clinical question, is how to modify this problem with therapy. My first recommendation is to phone-a-friend: your EP colleague. I can't give you a generic right answer because there isn't one. HFpEF patients often have serious comorbidities that have to be considered, things like polypharmacy and CKD and valvular HD and frailty. Maybe antiarrhythmic drugs are the right answer. Maybe ablation. And underused in some places is the 'pace and ablate' strategy. We see a lot more HFpEF these days, because people live longer and with more chronic illness. When AF occurs, it's serious. Take Mr. Rogers' advice and realize that we all need helpers in our lives, and please: call your EP friends.
