Research Translation Podcast
(Lipid) Love Is Blind
(upbeat music) Welcome back everybody to research translation. I am David Newman. It is currently Friday, March 14th, 2025. I'm back from, I am obviously back from my little mini break after Mardi Gras. Mardi Gras was a lot of fun and in fact my boys got to ride in one of the parades and that's normally just seems like a silly thing 'cause they were in silly costumes and I wasn't that jazzed about it but you know how to drive them around and bring the places and they hop on the float and I go to watch them with a bunch of friends as they ride by and for reasons unclear to me as soon as I saw them I burst into tears. So anyway it turned out to be a little bit more intense and emotional than I had expected. So today I figured we'd just get back to some old core type material, the same stuff that I usually do some basic research translation and I do have a little add on at the end just about some of the stuff I talked about last time 'cause I got a couple emails about it and some interesting discussions happened and a couple of people asked me about what the COVID connection was 'cause I had mentioned that but then not really fleshed that out. So the COVID connection to the like the harm reduction, abstinence debate, gonna briefly touch on that but before all that we get to talk about heart attacks and the new American Heart Association guidelines. So exciting. So here we go, heart attacks and cholesterol lowering. Believe it or not. (upbeat music) Lipid love is blind. New guidelines for heart attack treatment are smitten but their love is unrequited. Back in my day roughly the 16th century or so, Cupid was often depicted as a blindfolded angel and that is because love is blind. It is random and it is often blinding. Last week, the American Heart Association and the American College of Cardiologists professed their love and a new guideline for doctors on treating heart attacks. Among the top take home messages from the document, quote unquote, were give high dose statin drugs and other lipid lowering agents during or in the immediate wake of any heart attack. Which for anyone who knows the evidence is clearly an act of pure love, of raw emotion and of a wishful heart. Ah, but if only the statins loved them back. For starters, the now debunked theory underlying cholesterol treatment, the lipid hypothesis, says the cholesterol causes heart disease and therefore lowering it should prevent heart disease. So what's that got to do exactly with treating an active heart attack in progress? Isn't that kind of like rearranging chairs on a sunken ship or putting on the seat belt after the crash or closing the barn, whatever, you get it. But never mind how it works. The AHA has proof, they say. Giving high dose statins early in a heart attack reduces quote major cardiac events in the weeks that follow according to them. Ah, yes, yes. If true, this could actually be very important since heart attacks do indeed lead to a very vulnerable period that last weeks to months during which strokes and repeat heart attacks and deaths are actually much more common than in the regular population. And what is the proof for the statins you say? Well, the guideline cites four studies. And based on those four studies, the guideline classifies statins given during a heart attack as a one A drug or option. In other words, their highest recommendation from the strongest possible level of scientific proof. And now before we peruse the trials that they've cited, let us first acknowledge that the world's most comprehensive review on this very same topic, whether or not lipid lowering agents like statins are effective and useful and helpful in the throes of a heart attack or in the immediate wake. A review on that topic was published by the respected Cochrane group years ago and it found that the drugs have absolutely zero effect on deaths for their heart attacks or strokes. And by the way, there have been no new trials published since that Cochrane review. And in fact, the Cochrane group was very explicit about this. They reported that 18 trials were done on this topic. And of those 18, none of them showed that statins actually had a benefit in any of those objective measures that we just mentioned, heart attacks, strokes, or deaths. Not one of those trials. None, zero, zilchzip, not a, not, you get it. So what exactly is the AHA talking about? Well, it turns out in a few older trials, there was a tiny, and I'm being perfectly serious here, 1.5% reduction in unstable angina, as it's called, which is a nebulous and kind of cautionary and very presumptive diagnosis that cardiologists used to make when they saw patients with chest pain who had normal blood tests. In other words, no heart attack. Perhaps the theory went back then. The pain that those patients felt reflected subtle heart effects that the tests couldn't detect. And in fact, many of the older tests really did miss some important myocardial ischemia. In other words, poor blood flow to the heart muscle. So those older tests really did have that problem and that unstable angina diagnosis was a useful and important term and category. But starting in roughly the 2000s, when a new blood test took over called troponins and the old blood tests, which were called CPKs or creatinine phosphokinase, the CPKs and the CPK MBs and all of that whole category of blood tests sort of faded out. And a newer blood test called troponins came along. When the troponins came along, they were simply much, much, much more sensitive. And over the last 20 years, those troponins have become even more sensitive. But as soon as they phased in, they really were a total game changer and unstable angina started to fade out. So much so that unstable angina stopped being a category or at least was written about as something that should stop being a category by major authorities in the field of cardiology over a decade ago now. And the trials that we're talking about were done in the early 2000s, all the way up to 2010, 2013. So we're talking about a time period during which, in fact, the new blood tests were available and calling anybody unstable angina was probably a mistake to begin with because in fact, if they were having myocardial ischemia or true heart-related pain, it would have been detected by the troponins being used during that trial. All of which is a kind of convoluted and long way of getting to the point that the only actual benefit that they statistically or in any other fashion ever claimed existed about giving high-dose statins or other lipid lowering agents during a heart attack or in the immediate wake of a heart attack was in a category that is no longer relevant. It was even then during those trials, a dubious and judgment-based category that just doesn't even exist anymore. It's literally not a thing. So whatever that benefit was, it's not a thing anymore. And it probably wasn't even during the trials. Now, as for the four sort of cherry-picked studies that the guideline references, well, that is Cupid's work. The first is a comparison of high-dose versus low-dose statins, not placebo. In other words, it's not testing whether or not high-dose statins or lipid lowering agents actually benefit. It was looking at higher versus lower-dose statins. And even that study found that the higher doses had no impact on death strokes or heart attacks. The second study that they cite tested 16 weeks of statins versus, thank the Lord, a placebo after a heart attack. But again, even that study found no benefit other than a small reduction in the now obsolete category of unstable angina. The third study found no benefit with four months of statins over a placebo, but it did find an increase in serious muscle damage due to the statins. And then the fourth study that they quote or reference is actually a meta-analysis of statins versus other statins trials. And it's doubly irrelevant because it actually includes studies that were totally unrelated to acute heart attacks. So the new guideline is deeply in love. And blind as bats, the authors claim to review the evidence and even made gestures that looked scientific, like citing studies and using terms like major adverse cardiac events, scary. But the saddest part about all of this is that the statins didn't seem to love them back. Even for patients experiencing an extremely vulnerable and high risk period of cardiac risk, for whom the drugs really should be life-saving and should be easily, easily fit, fit to purpose for preventing further strokes and heart attacks and deaths. In that period, those drugs should work. They didn't. Those drugs failed to validate the lipid hypothesis, even in the highest risk period, when they should be the easiest to find a benefit. They failed to reduce heart attacks or deaths. I think one might say that the statins broke their vows, and that love is unrequited. Although it is worth pointing out that based on the guidelines committee disclosures, more than a third of the committee that wrote the guidelines has financial ties to the drug makers that sell lipid-lowering drugs. So maybe love isn't totally blind, after all. All right, that'll do it. Feel free to ask me any questions about that statin stuff. You know, it's a pet project of mine, and it has been for decades now. I think the lipid hypothesis is interesting and to clarify, I don't think that the statins are probably killers as best I can tell, although they do seem to increase diabetes. And there was, for years, a real concern about whether or not they might increase hemorrhagic strokes, meaning bleeds in your brain. If so, that was probably rare, and it hasn't really easily been found in trials or even in observational data. So if there is a bump there, it's probably super, super tiny. So I'm not claiming the statins are killers. I am claiming that for primary prevention, they don't work. They simply don't have the effect that most people think or want, they don't prevent people from dying. That seems to be very, very clear in the data. But for secondary prevention among people who have known heart disease, and that includes people who have had a heart attack, there is a benefit that you can find in the trials. So even with this acute heart attack treatment thing, I'm not saying that people should never be put on statins. After a heart attack, it's not unreasonable to start optimizing everything that you can optimize in the pantheon of cardiac risk factors. And so addressing cholesterol, if it's quite high, seems like a reasonable thing to do. And the data supports it a little bit. There is a small reduction in heart attacks, maybe even a small reduction in deaths in the studies that look at people who are known to have heart disease. So it's not crazy to take statins, particularly if you're not getting side effects from them. It's not crazy at all to take them if you have known heart disease or vascular disease. That's not crazy, and I don't mean to claim that it is. But it is crazy to believe that the statins, which are focused on cholesterol, somehow validate the lipid hypothesis, which is the whole notion that cholesterol causes heart disease and that treating it will vanquish heart disease. If that was true, then why didn't the statins vanquish heart disease, and why in so many primary prevention studies, as I've written about before, why didn't they save lives and have more salutary effects? So the fact that they are something that any cardiology group would look at and say, oh yeah, yeah, we need to give these in the throes of a heart attack, that's a little bit loopy. That's a crazy thing to even suggest because in the throes of a heart attack, there really are good treatments that need to be focused on and that really are important, and that really do save lives. So when you start focusing on the cholesterol problem, which is supposed to be a prevention problem, not a treatment problem for heart attacks, it seems to me you've gone off the deep end a little bit. And it turns out, their rationale, which is in that vulnerable period, there was gonna be live saved and strokes and heart attacks avoided, that wasn't true. And those studies proved it beyond all shadow of a doubt. All right, I've pounded that one enough. I wanna briefly touch on the thing that I talked about last time, which is the harm reduction versus abstinence. I think everybody knows this now, but harm reduction classically would be something like in terms of public health messaging and interventions, it would be something like giving out clean needles to IV drug abusers. That's a harm reduction attempt because it reduces Hep C and HIV transmission and makes the use of drugs cleaner. And frankly, probably a little bit easier. Harm reduction is a kind of a softy approach that says we meet people where they are and we try and reduce the harm that comes from whatever the problem is that we're seeing on a public health scale. And if it's IV drug abuse, clean needles is one way to do it. So is clean places to inject drugs, which there are many cities that do that as well, offer clean areas for drug injection, where it's actually overseen and overdose becomes very, very difficult to impossible to do because there are people sort of watching over and supervising to make sure that in this clean environment, there isn't going to be an overdose and giving out clean needles, another way to reduce the harms of IV drug abuse. The abstinence approach, the other polar opposite, at least in the universe of public health interventions, the polar opposite to harm reduction is abstinence, where you create mandates and those mandates are focused on making it really hard to get needles, making it really hard to find places to actually use IV drugs. And if you have to go use a dirty needle and do it in a dirty place, maybe that will just keep you from doing IV drugs in the future. And there are lots of arguments for why these two approaches have worked or not worked in many different scenarios and settings. But the point that I made last time we talked was that there's a difference between harm reduction and abstinence and that there's a debate that's happening there related to vaping versus smoking. And the thing about vaping versus smoking that's fascinating is that vaping is a harm reduction approach, right? You can keep people on nicotine, but hand them a vape pen or an e-cigarette and say, hey, this way you're not going to get the lung cancer, you're not going to get the other cancers you would have. So we're reducing harm, but you're going to keep being addicted to nicotine versus the abstinence approach to smoking, which is we make it hard to smoke, we put a whole bunch of taxes on trying to buy cigarettes so that it's really expensive. We make it illegal to do in restaurants and in certain public places, et cetera, et cetera. That's more the abstinence side. The thing that's kind of interesting about that is that the abstinence side for smoking worked really, really well. And it brought down smoking a lot over the years. And now this harm reduction approach is hard for people to sort of accept and understand. But there is an oddity related to COVID and this was the point that I wanted to make that has to do with the weird sort of pendulum swings of politics and culture and everything else, which is just this. During the COVID pandemic, we had a lot of missteps. There were missteps by every country. America certainly had missteps in its public health approach in various ways and we can look back at them and hopefully learn from them and hopefully move forward and progress so that we do things a little bit better next time. But regardless of what you think the missteps were or weren't, clearly one of the big debates that came out of COVID and one of the big ongoing cultural issues that came out of the COVID pandemic was the fact that people reacted very, very poorly to mandates. People felt that mandates, whether it was masks or getting vaccinated, that mandates were inappropriate. They were a breach of civil liberties and they were a problem. And I think there's a very obvious, very conspicuous, whole political movement that is sort of attached to that notion. And that political movement has a lot of really strong points in terms of public health apparatus and public health truth telling versus sort of questionable not so truth telling. We talked last time about how, for instance, if you were an abstinence sort of public health person, you might have been involved in the 1950s in developing the movie, Reefer Madness, which is a hilarious and fantastic movie. Now it just looks like satire, but at the time it was dead serious, but it was a movie designed to keep kids from getting involved in marijuana smoking. And looking at it now, we know that marijuana is not physically addictive in quite the same way that cigarettes and heroin or other hard drugs are. We know that there are substantially fewer harms to marijuana and that's why it's now legal in so many places, but if you watch Reefer Madness, you would think that this is not just crack cocaine, but a much, much worse version, maybe like a fentanyl or something like that, that we know is really dangerous and probably overwhelmingly bad and needs to be avoided. The abstinence approach that came with Reefer Madness is kind of like a lot of what we saw with the COVID stuff in the sense that the messaging got a little overinflated. You need to wear your masks or everybody's gonna die. And then we found out when we saw the data that not only do masks probably not work very well, but even if they do work, they only work a little. They just work a tiny bit and I've reviewed that data. You can go back to my prior post to see that data. I explored that data in depth. So if you're wondering about what that data says, you can go back to that one. That was a fun one to go through all of the different studies, but the point is we found out that the public health messaging surrounding masking was kind of misleading. It wasn't straight truth telling. And I think at least my perception is that as it relates to abstinence approaches, it is often true that there needs to be some fear mongering. There needs to be some scare tactic that goes along in order for it to be effective. And that was true with smoking. And with smoking, the fear tactics, the fear mongering and the scare tactics, they worked. They worked really well, they helped to reduce smoking down to a much smaller percentage than it was, and it probably saved millions and millions of lives in terms of heart attacks, cancers and everything else. So those were actually valuable, effective approaches to public health related to smoking. And they were abstinence based, they were mandate based, and they used exaggeration and going beyond the truth to try and make something seem even a little worse and more scary than it was. This is, I think, what people saw in the COVID pandemic and what many people still looking back at it, object to and are frustrated by or are scared about for future public health issues. Did we oversell it on masking? Yeah, maybe. Was it oversold when it came to like school lockdowns and that kind of thing? Yeah, probably. Did we oversell the vaccine? That's a much more complicated and tricky issue. And I'm not gonna get into that here, but all I will say is that it's a debate that people are having all the time now. The vaccine probably saved a lot of lives, but whether or not the vaccine mandates were appropriate, particularly for certain ages and groups who had very, very low risk of ever dying of COVID, is a much different kind of a question. So that was the connection that I was trying to make about the harm reduction in abstinence stuff, is with the political and cultural pendulum swings that we're seeing in the sort of wake of the pandemic. I think one of the most important ones, one of the ones that is affecting policy, it's affecting all kinds of public health approaches and the way people see and wanna see transparency in government and in public health issues. One of those is the way COVID was handled and the kind of truth telling versus exaggeration, mandate versus suggestion, abstinence versus harm reduction, kind of approaches that were taken in the pandemic. So when I was talking about harm reduction versus abstinence, that was the point I sort of wanted to get to and I didn't wanna go too long, so I didn't get into it at length after I talked about vaping versus smoking, but I'm coming back to it now just so people can understand what that one COVID connection was. So you can understand what the cultural issue is that's happening in the public health universe right now, which is this debate about whether to do mandates or to really respect civil liberties more and let people sort of, you know, pick their poison in a way or make their decisions and live with those decisions. So that was the stuff I wanted to get to that I hadn't gotten to before. That'll cover it for me. Let me know if you have any questions, fire any comments at me, as always talk to you soon. Bye. (upbeat music) (upbeat music)