WEBVTT - Ep 218 The Lowdown on Statins 0:00:00.160 --> 0:00:03.320 I was born into a rural farming family in northern Japan, 0:00:03.720 --> 0:00:06.760 where I lived for seventeen years with my extended family, 0:00:07.000 --> 0:00:11.760 including grandparents, parents, three brothers, and two sisters. My grandfather, 0:00:11.840 --> 0:00:14.480 who had an interest in medicine and science, was a 0:00:14.520 --> 0:00:17.759 great home teacher to me thanks to his influence. At 0:00:17.800 --> 0:00:20.680 the age of eight, I dreamt of becoming a scientist. 0:00:21.200 --> 0:00:23.960 After finishing high school in Akida, I entered to Hoku 0:00:24.079 --> 0:00:28.000 University's College of Agriculture in Sendai in nineteen fifty three. 0:00:28.440 --> 0:00:31.160 As a student, I was deeply impressed by the knowledge 0:00:31.160 --> 0:00:34.519 that antibiotics had saved the lives of many patients with 0:00:34.560 --> 0:00:39.480 infectious diseases. I received a PhD degree from Tohoku University 0:00:39.560 --> 0:00:43.239 in nineteen sixty six. At this point, I became interested 0:00:43.360 --> 0:00:48.360 in cholesterol biosynthesis. I eventually studied from September nineteen sixty 0:00:48.400 --> 0:00:51.720 six to August nineteen sixty eight at the Albert Einstein 0:00:51.800 --> 0:00:55.480 College of Medicine in New York. At that time, coronary 0:00:55.480 --> 0:00:57.800 heart disease was the main cause of death in the 0:00:57.880 --> 0:01:02.360 United States. The number of people with hypercholesterolemia, a precursor 0:01:02.400 --> 0:01:05.920 to coronary heart disease, was said to exceed ten million. 0:01:06.560 --> 0:01:09.560 My experience of living in New York made me realize 0:01:09.600 --> 0:01:13.760 the importance of developing a cholesterol lowering drug. After coming 0:01:13.800 --> 0:01:17.520 back to Tokyo in nineteen sixty eight, Sankyo Research Laboratories 0:01:17.560 --> 0:01:20.200 gave me an opportunity to work on a project of 0:01:20.200 --> 0:01:24.240 my own. Choosing I speculated that fungi like molds and 0:01:24.319 --> 0:01:31.040 mushrooms would produce antibiotics that inhibited hmg CoA reductase compactin 0:01:31.520 --> 0:02:09.120 seemed to be a wonderful gift from nature. 0:02:19.760 --> 0:02:24.560 I want to know everything more that you're about to 0:02:24.600 --> 0:02:27.480 tell me. You from that story, you will, you will. 0:02:27.600 --> 0:02:32.360 So that was excerpted from actually two different articles written 0:02:32.560 --> 0:02:36.880 by Akira Endo, who was the father of statins. He 0:02:37.840 --> 0:02:41.760 discovered the first statn and he has written about this 0:02:41.800 --> 0:02:44.560 in multiple different places. But this was from two papers, 0:02:44.600 --> 0:02:47.119 one from two thousand and eight and one from twenty ten, 0:02:47.280 --> 0:02:50.119 and we'll have them in our show notes. But yeah, 0:02:50.160 --> 0:02:54.320 I loved, I love, just like I'm still amazed at 0:02:54.440 --> 0:02:57.359 the logic link leap that it is. 0:02:57.520 --> 0:02:59.160 That's what I that's what I want. I want so 0:02:59.240 --> 0:03:01.280 much more of that. Like what was he thinking and 0:03:01.320 --> 0:03:04.520 how did he piece these things together? And like I 0:03:04.560 --> 0:03:06.440 want to know it all because I'm really, I'm really, 0:03:06.880 --> 0:03:10.799 I'm really excited for this episode. Erin, should we. 0:03:10.280 --> 0:03:13.959 Yeah, me too, Me too, It's going to be great. Hi. 0:03:14.240 --> 0:03:17.200 I'm Aaron Welsh and I'm Erin allman Updyke. 0:03:16.919 --> 0:03:18.920 And this is this podcast will kill you. 0:03:19.280 --> 0:03:23.800 Welcome to Cholesterol Part two, Part two where we love in. 0:03:23.720 --> 0:03:30.120 Blue Blue Yes, good ones. Yeah, yeah to this. 0:03:30.280 --> 0:03:32.600 So if you didn't listen to last week's episode, you 0:03:32.680 --> 0:03:35.840 really should because it'll give you some great foundation for 0:03:36.000 --> 0:03:39.280 understanding why cholesterol does what it does in our bodies 0:03:39.320 --> 0:03:44.680 and why certain levels of different types of cholesterol mean disease. 0:03:45.600 --> 0:03:48.960 I know that we're biased, but I think it's a 0:03:48.960 --> 0:03:53.280 great episode. You haven't listened to it, check it out. 0:03:53.360 --> 0:03:55.680 And then today we're going to build on so much 0:03:55.680 --> 0:03:59.200 of that and talk about how we deal with high 0:03:59.240 --> 0:04:01.120 cholesterol and how we figured out how to deal with it, 0:04:01.200 --> 0:04:04.440 and it's going to be really great. Yes, But before 0:04:04.440 --> 0:04:06.840 we can start, it's quarantine time. 0:04:07.160 --> 0:04:11.280 It is once again we are drinking plack attack. 0:04:13.480 --> 0:04:13.760 Again. 0:04:13.880 --> 0:04:16.120 Are we attacking plaque? Is plac attacking us? 0:04:16.200 --> 0:04:20.320 A little bit of both? Yes, with black clack attack. 0:04:20.680 --> 0:04:24.000 It's a pretty it's a pretty delicious, straightforward, nothing to 0:04:24.080 --> 0:04:29.400 do with cholesterol, just delicious. It's blueberries smashed with lemon 0:04:29.480 --> 0:04:34.080 juice and uh club soda and simple syrup. 0:04:34.320 --> 0:04:35.080 And it meant. 0:04:37.720 --> 0:04:40.720 I haven't putten down and yet it's like not, I 0:04:40.760 --> 0:04:41.640 just didn't pull it up. 0:04:41.680 --> 0:04:44.240 So we'll post the full recipe on our website, this 0:04:44.240 --> 0:04:46.880 podcast with Killy dot com on our social media's which 0:04:46.920 --> 0:04:54.000 include Instagram and blue Sky and Facebook, Facebook and TikTok. 0:04:54.160 --> 0:04:56.760 I don't know if it's there on TikTok though, listen, 0:04:57.000 --> 0:04:58.560 just follow us there. 0:04:59.040 --> 0:05:01.600 You'll see what we're up to here, Absolutely you will. 0:05:01.880 --> 0:05:05.680 Yeah, you can also see a little bit of what 0:05:05.680 --> 0:05:07.680 we're up to by going to our website. 0:05:07.960 --> 0:05:10.320 This podcast will kill You dot com. It's got yeah, 0:05:10.360 --> 0:05:11.960 not not quite, but like it's got. 0:05:12.000 --> 0:05:15.280 It's got resources, right, got lots. We've got all of 0:05:15.320 --> 0:05:18.400 the papers we use for all of our episodes. It's 0:05:18.440 --> 0:05:22.680 got links to our bookshop dot org, affiliate page, music 0:05:22.680 --> 0:05:28.040 by Bloodmobile, links to merch links to Patreon, it's got 0:05:28.080 --> 0:05:31.280 a first hand account, form of contact us form things 0:05:31.600 --> 0:05:33.640 that everything explore. 0:05:33.480 --> 0:05:35.599 Everything we could think of is there. 0:05:36.400 --> 0:05:37.120 Yeah. 0:05:37.160 --> 0:05:40.000 Thank you to everyone who has rated and reviewed and 0:05:40.040 --> 0:05:44.800 subscribed on your podcatcher or YouTube of choice. 0:05:45.240 --> 0:05:48.359 Yes, yes, we appreciate it. We do. I know, we know. 0:05:48.440 --> 0:05:50.719 There are so much media out there that you can consume, 0:05:50.880 --> 0:05:54.240 and so it means truly, it means so much to us. 0:05:54.320 --> 0:05:57.000 It feels surreal that you're choosing to spend any time 0:05:57.040 --> 0:05:57.440 with us. 0:05:57.640 --> 0:05:59.680 I don't know. Every time and says they listen, I'm 0:05:59.720 --> 0:06:05.000 like to me to us, what really, Yeah, it's incredible, 0:06:05.760 --> 0:06:09.520 thank you, thank you. Okay, Aaron, tell me about this 0:06:09.560 --> 0:06:11.599 guy and how he came up with statins and everything else. 0:06:11.640 --> 0:06:15.040 Okay, absolutely, let's take a quick break and we'll do 0:06:15.080 --> 0:06:15.560 all of that. 0:06:34.560 --> 0:06:36.200 Last week I took us. 0:06:36.080 --> 0:06:38.800 Through the story of cholesterol and how it earned its 0:06:38.800 --> 0:06:43.080 reputation as a major cause of cardiovascular disease. Over the 0:06:43.120 --> 0:06:46.440 course of about seven decades, from the nineteen tens to 0:06:46.560 --> 0:06:50.279 the early nineteen eighties, researchers put the pieces of the 0:06:50.360 --> 0:06:54.159 cholesterol puzzle together using a wide range of studies. We 0:06:54.240 --> 0:06:58.920 had experimental ones like A. Nich Coow's athrosclerotic rabbits. There 0:06:59.040 --> 0:07:04.799 were analytical epidemiological ones like the Framingham Heart study, genetic ones, 0:07:04.839 --> 0:07:08.720 and mechanistic ones like Brown and Goldstein's Nobel Prize winning 0:07:08.800 --> 0:07:14.240 work characterizing the LDL receptor, lots of different studies. 0:07:14.480 --> 0:07:16.120 Different lines of evidence. 0:07:16.240 --> 0:07:20.800 Yes, yes, And this week I'm going to pick up 0:07:20.880 --> 0:07:24.480 with the final piece of this puzzle, cholesterol lowering drugs 0:07:24.520 --> 0:07:27.680 and some of the controversy that surrounds them. 0:07:27.960 --> 0:07:29.360 By the nineteen seventies, much of. 0:07:29.360 --> 0:07:34.160 The cardiology world, like researchers, physicians, and institutes, they saw 0:07:34.200 --> 0:07:38.240 the link between cholesterol and cardiovascular disease as a done deal. 0:07:38.560 --> 0:07:42.800 This is established, Okay, now let's proceed from here. But 0:07:42.960 --> 0:07:47.560 that knowledge didn't reach beyond that realm of experts, and 0:07:47.720 --> 0:07:53.120 many physicians remained either skeptical or oblivious to this new knowledge. So, 0:07:53.200 --> 0:07:57.600 for example, a nineteen eighty three study of internists in 0:07:57.600 --> 0:08:02.600 the US showed that fifty percent did not recommend any therapy, 0:08:02.680 --> 0:08:08.160 including diet, for cholesterol lowering unless levels were over three hundred. 0:08:08.880 --> 0:08:11.360 Fast total in like the mid eighties. 0:08:11.400 --> 0:08:12.560 Based nineteen eighty three. 0:08:12.680 --> 0:08:17.360 Yeah, wow, yeah, it just it also shows how quickly 0:08:17.640 --> 0:08:18.560 things have shifted. 0:08:19.120 --> 0:08:22.840 Yeah, which is so interesting also because I just think about, 0:08:22.880 --> 0:08:26.920 like we've talked about before, how slow changes in medicine, 0:08:26.960 --> 0:08:30.800 and like, there are plenty of people practicing today who 0:08:30.840 --> 0:08:33.040 were probably practicing in the eighties, like getting trained in 0:08:33.040 --> 0:08:35.800 the eighties, so that it's just so interesting. 0:08:36.040 --> 0:08:37.160 Yeah, yeah, it is. 0:08:37.240 --> 0:08:40.240 It is really interesting, and I think it also like, 0:08:41.200 --> 0:08:44.640 okay for you today this I wanted to share more 0:08:44.679 --> 0:08:46.440 of these numbers because I think it'll come as a 0:08:46.440 --> 0:08:48.520 real like double take. 0:08:48.840 --> 0:08:49.640 Yeah, exactly. 0:08:50.280 --> 0:08:50.360 So. 0:08:51.280 --> 0:08:53.840 Of that of those fifty percent who wouldn't recommend any 0:08:53.840 --> 0:08:58.560 therapy unless over three hundred hundred, nearly half said no 0:08:58.760 --> 0:09:02.880 therapy unless levels or over three point forty three, and 0:09:02.960 --> 0:09:06.000 twenty seven percent of those said that they would never 0:09:06.080 --> 0:09:10.000 recommend drug treatment under any circumstances for cholesterol. 0:09:10.040 --> 0:09:10.720 For cholesterol. 0:09:12.600 --> 0:09:18.120 Yeah, So what would it take for high blood cholesterol 0:09:18.200 --> 0:09:21.840 to be seen as a pressing public health issue, at 0:09:21.920 --> 0:09:25.920 least among all medical professionals, if not the general public. Yeah, 0:09:26.360 --> 0:09:32.440 an available treatment and evidence that intervention worked. Those two 0:09:32.559 --> 0:09:35.520 things would emerge at nearly the same time in the 0:09:35.559 --> 0:09:36.640 early nineteen eighties. 0:09:37.080 --> 0:09:39.280 Arin. I don't want to interrupt you because I'm loving this. 0:09:39.360 --> 0:09:41.600 But as a side note, you know what we should 0:09:41.640 --> 0:09:45.480 do an episode on tell Me evidence based medicine. 0:09:45.640 --> 0:09:47.199 Yeah, okay, because. 0:09:46.880 --> 0:09:48.360 That is a really new thing. 0:09:50.600 --> 0:09:52.000 Wait wait, wait, what do you mean by that is 0:09:52.040 --> 0:09:52.840 a really new thing? 0:09:53.200 --> 0:09:56.599 I mean The idea that we should only make recommendations 0:09:56.600 --> 0:10:00.000 for things if we have evidence to support them is 0:10:00.120 --> 0:10:03.280 a relatively new concept in the history of medicine, and 0:10:03.320 --> 0:10:03.680 I mean. 0:10:03.760 --> 0:10:06.600 Really humoral theory has tons of support. 0:10:06.720 --> 0:10:11.160 Erin, sorry to cite. 0:10:11.280 --> 0:10:13.480 No, we should definitely do We should definitely do that. 0:10:13.760 --> 0:10:16.560 We've had ideas to do things like randomized control trials 0:10:16.559 --> 0:10:17.080 as well. 0:10:17.200 --> 0:10:20.640 Yes, and I know, just like, yeah, there's too long 0:10:20.679 --> 0:10:21.120 of a list. 0:10:21.400 --> 0:10:23.880 We have such a long list. It's great. It's a 0:10:23.960 --> 0:10:24.679 good problem to have. 0:10:24.800 --> 0:10:26.360 Okay, we're in the eighties. 0:10:26.480 --> 0:10:27.240 We're in the eighties. 0:10:27.320 --> 0:10:29.640 A lot of people are like, no, dude, give me 0:10:29.679 --> 0:10:33.439 some evidence, right, And the cardiologists or the cardio cardiology 0:10:33.559 --> 0:10:37.400 research people are like, oh my god, this we're in trouble. 0:10:37.480 --> 0:10:38.080 We're in trouble. 0:10:38.440 --> 0:10:44.160 Okay, So we needed treatment and proof that any sort 0:10:44.200 --> 0:10:46.120 of intervention worked, whether it was the treatment or just 0:10:46.240 --> 0:10:50.840 lowering cholesterol that that led to actual results. Those two things, 0:10:50.880 --> 0:10:54.520 a treatment and proof of intervention, would emerge at nearly 0:10:54.600 --> 0:10:55.319 the same. 0:10:55.120 --> 0:10:56.680 Time in the early nineteen eighties. 0:10:56.840 --> 0:11:00.480 Okay, so at the National Institutes of Health PLIANS had 0:11:00.480 --> 0:11:03.920 been underway since nineteen seventy for a large scale study 0:11:03.960 --> 0:11:06.920 that would measure the impact of cholesterol lowering drugs on 0:11:07.000 --> 0:11:11.840 cardiovascular disease. Previous studies had shown that high blood cholesterol 0:11:11.920 --> 0:11:15.920 levels overall correlated to higher rates of heart attacks, but 0:11:16.000 --> 0:11:19.560 the next step was showing that lowering those levels would 0:11:19.559 --> 0:11:21.800 then lead to fewer cardiac events. 0:11:21.960 --> 0:11:25.400 Exactly, we know that there's this positive correlation between high 0:11:25.480 --> 0:11:28.520 levels and bad outcomes. Can we change that? 0:11:28.840 --> 0:11:31.080 Can we change that? Can we do something? 0:11:31.080 --> 0:11:33.360 Because then that would also suggest it would be a 0:11:33.600 --> 0:11:35.679 very great evidence for causation. 0:11:35.320 --> 0:11:37.800 For causation, exactly, Yeah. 0:11:37.160 --> 0:11:40.560 So the Coronary Primary Prevention trial was designed to do 0:11:40.679 --> 0:11:44.679 exactly that show this line of causation. The study enrolled 0:11:45.120 --> 0:11:48.760 three eight hundred men aged thirty five to fifty nine 0:11:48.880 --> 0:11:52.640 with high total blood cholesterol so two sixty five or higher, 0:11:53.400 --> 0:11:56.600 and they were to be followed for at least five years. 0:11:57.120 --> 0:12:00.000 The treatment group was supposed to take a cholesterol lowering drug, 0:12:00.000 --> 0:12:04.400 a cholestyramine. Statins weren't yet approved at this point, and 0:12:04.600 --> 0:12:08.960 all participants were instructed to follow a cholesterol lowering diet. Okay, 0:12:09.320 --> 0:12:12.440 knowing what we know today about the link between cholesterol 0:12:12.520 --> 0:12:15.280 and cardiovascular disease, a trial like this would not be 0:12:15.320 --> 0:12:18.319 conducted in the same way where you would withhold drugs 0:12:18.400 --> 0:12:21.480 from one group, but at the time the evidence was 0:12:21.480 --> 0:12:24.680 not as firm, especially for medication, and so that's why 0:12:24.720 --> 0:12:28.520 it went forward. By the early nineteen eighties, after an 0:12:28.520 --> 0:12:31.920 average of seven years follow up for each participant, the 0:12:32.000 --> 0:12:37.560 results were in and they were unambiguous. Lowering blood cholesterol 0:12:37.640 --> 0:12:40.920 in high risk men reduced the risk of heart attack. 0:12:41.520 --> 0:12:42.800 Those who took period. 0:12:43.360 --> 0:12:45.880 Those who took the full dose of treatment had a 0:12:45.880 --> 0:12:48.959 thirty five percent reduction in total cholesterol and a forty 0:12:49.080 --> 0:12:53.200 nine percent decline in the rate of cardiac events. But 0:12:53.559 --> 0:12:55.920 even those who didn't follow the treatment to a t 0:12:56.520 --> 0:13:01.960 like the cholestyramine, had lowered cholesterol in heart attacks. Now, 0:13:02.040 --> 0:13:05.320 the study was not perfect, but when the results were 0:13:05.320 --> 0:13:08.640 published in nineteen eighty three, it led to a moment 0:13:08.679 --> 0:13:11.079 of reckoning for the field, like it was no longer 0:13:11.200 --> 0:13:15.840 enough to simply acknowledge that this relationship exists. Something had 0:13:15.880 --> 0:13:19.680 to be done about it right, and that's something was 0:13:19.720 --> 0:13:23.280 to be decided at the nineteen eighty four NIH Consensus 0:13:23.280 --> 0:13:26.600 Development Conference. So there was a panel of experts at 0:13:26.600 --> 0:13:28.840 this conference who came up with a set of guidelines 0:13:28.880 --> 0:13:32.360 for what would be considered high or low blood cholesterol 0:13:34.000 --> 0:13:37.200 for certain ages and how that fell out, and also 0:13:37.360 --> 0:13:41.120 diet and exercise recommendations for how to reduce cholesterol. They 0:13:41.200 --> 0:13:45.560 also advocated for a nationwide educational program in which general 0:13:45.600 --> 0:13:48.560 practitioners as well as the general public were taught about 0:13:48.559 --> 0:13:50.080 the importance of cholesterol. 0:13:50.400 --> 0:13:51.959 I love that. YEP. 0:13:52.400 --> 0:13:55.600 This conference had a substantial impact over the next decade, 0:13:55.679 --> 0:14:00.079 with the percentage of physicians pointing out LDL as an 0:14:00.080 --> 0:14:03.600 important marker for the risk of heart disease that increased 0:14:03.960 --> 0:14:07.240 from nineteen eighty six to nineteen ninety five, from thirty 0:14:07.280 --> 0:14:09.440 four percent to seventy five percent. 0:14:10.360 --> 0:14:12.959 So like in nineteen eighty six, only like. 0:14:12.960 --> 0:14:15.920 Thirty percent said your physicials would be like. 0:14:16.520 --> 0:14:19.160 Yeah, okay, and then ninety okay, ninety. 0:14:18.960 --> 0:14:20.920 Five, and then it was seventy five percent in nineteen 0:14:21.000 --> 0:14:24.040 ninety five, better than before, better than before. At the 0:14:24.120 --> 0:14:27.120 time that the panel was making these recommendations, there still 0:14:27.360 --> 0:14:31.640 wasn't really a good cholesterol lowering medication available, So the 0:14:31.640 --> 0:14:34.400 one that they had used in the study, colostyramine, came 0:14:34.440 --> 0:14:37.240 in a sandy powder which you had to mix into 0:14:37.280 --> 0:14:39.760 water and consume throughout the day, so you had to 0:14:39.760 --> 0:14:42.280 consume twenty four grams a day, was like the goal 0:14:42.440 --> 0:14:44.479 in the study, which was like six. 0:14:44.280 --> 0:14:47.480 Packets of this or something like that. No one's chasing that. 0:14:47.800 --> 0:14:49.200 It was quite a heavy. 0:14:48.920 --> 0:14:51.800 Lift, and it was made even more daunting by the 0:14:51.880 --> 0:14:55.280 gi upset that it caused in many you know, bloating, diarrhea. 0:14:54.760 --> 0:14:55.960 Constipation and stuff like that. 0:14:56.240 --> 0:14:59.920 Yeah, so there was clearly a need for a safe, effective, 0:15:00.000 --> 0:15:05.160 an easy medication to lower cholesterol. Fortunately, researchers were well 0:15:05.240 --> 0:15:09.240 underway in their quest for such a wonder drug in 0:15:09.320 --> 0:15:13.720 nineteen seventy one. The first hand account provider for this episode, 0:15:13.720 --> 0:15:17.000 doctor Akira Endo, was working as a research biochemist at 0:15:17.000 --> 0:15:20.920 the Japanese pharmaceutical company Sanchio when he got an idea. 0:15:21.680 --> 0:15:26.680 Endo had long been fascinated with Alexander fleming serendipitous discovery 0:15:26.720 --> 0:15:30.920 of penicillin, and after a research in New York, he 0:15:30.960 --> 0:15:35.440 had become intrigued by this problem of hypercholesterolemia, and he 0:15:35.600 --> 0:15:41.600 figured that, okay, if fungi produced antibacterial compounds like penicillin 0:15:41.720 --> 0:15:44.640 to compete with other fungi, it's not like they produce 0:15:44.680 --> 0:15:47.200 it because they're like, oh, humans could use this, No, 0:15:47.920 --> 0:15:52.440 they right, it's part of the ecology. 0:15:52.320 --> 0:15:55.000 Of their penicillium. 0:15:55.240 --> 0:15:57.560 Then it's possible that they would produce other types of 0:15:57.600 --> 0:16:01.720 compounds that would interfere with or help them compete against 0:16:01.800 --> 0:16:05.200 fungi in other ways, such as maybe a compound that 0:16:05.600 --> 0:16:07.680 interferes with cholesterol. 0:16:07.120 --> 0:16:13.360 Collection because cholesterol is so essential for life. Yeah, fascinating. Yeah, 0:16:13.680 --> 0:16:17.000 So he just was like, bro Fleming did this. Once 0:16:17.280 --> 0:16:21.480 Fleming did this, Maybe there's I can find something here 0:16:21.600 --> 0:16:23.200 because cholesterol is so important. 0:16:23.520 --> 0:16:25.760 Yes, And he was, I mean part of the thing too. 0:16:25.800 --> 0:16:27.760 He was like, he was like, fungi is all I knew. 0:16:28.240 --> 0:16:30.200 So that's where I looked. 0:16:30.560 --> 0:16:30.840 Hah. 0:16:31.120 --> 0:16:34.000 But it also like that that logic is very clear, 0:16:34.080 --> 0:16:37.160 but it had no direct support from any studies, Like 0:16:37.200 --> 0:16:39.920 there was penicillin and the fact that we found other 0:16:39.960 --> 0:16:43.000 antibiotics through this sort of like oh, this thing is 0:16:43.040 --> 0:16:48.600 producing this thing that kills this bacteria or this fungi 0:16:48.680 --> 0:16:50.480 in the environment, but like, yeah, but. 0:16:50.480 --> 0:16:53.040 To think of it for use on cholesterol, like that's 0:16:53.040 --> 0:16:57.640 so that's so interesting that his brain just did that right, Yeah. 0:16:57.720 --> 0:17:01.360 And found he was right about it. Yeah. I mean, 0:17:01.400 --> 0:17:03.720 so it took a while. It took two years. 0:17:03.840 --> 0:17:06.800 He and his colleagues over that time screened six thousand 0:17:06.920 --> 0:17:11.320 strains of microbes searching for a compound with cholesterol lowering 0:17:11.320 --> 0:17:15.159 properties like searching for a needle in a haystack. Really wow, 0:17:15.400 --> 0:17:18.280 And the first hit on this was less of a 0:17:18.320 --> 0:17:19.200 needle and more of. 0:17:19.160 --> 0:17:22.960 A crochet hook, but the second. 0:17:22.800 --> 0:17:26.320 Was exactly what they were looking for. A compound came 0:17:26.480 --> 0:17:32.320 from the mold penicillium citrinum with another penicillium, and they 0:17:32.400 --> 0:17:35.480 named it Compactin, also known as mevastatin later. 0:17:35.640 --> 0:17:35.800 Ok. 0:17:36.080 --> 0:17:41.760 Yeah, and this was the first statin h Yeah. 0:17:41.920 --> 0:17:45.560 So over the next several years, Endo and other researchers 0:17:45.560 --> 0:17:50.600 at Sanchio tested compact in safety, efficacy, and commercial viability, 0:17:50.840 --> 0:17:55.320 and other pharmaceutical companies got wind of this, like Merk, 0:17:55.400 --> 0:17:57.679 who was like, can we get a sample of that 0:17:57.720 --> 0:17:59.520 and see what's going on? And then they were like, 0:17:59.560 --> 0:18:01.320 how did you find this? Well, we're going to look 0:18:01.359 --> 0:18:04.040 for our own statin in the same way. They had 0:18:04.040 --> 0:18:07.240 to kiss way fewer frogs, only eighteen before they found 0:18:07.320 --> 0:18:08.800 their prints. 0:18:08.240 --> 0:18:10.600 In LoVa statin in nineteen seventy eight. 0:18:11.160 --> 0:18:16.199 Oh, competition, competition, Yeah, and then there's some there's like 0:18:16.240 --> 0:18:18.320 a lot. There is so much more to the story 0:18:18.400 --> 0:18:23.040 of like statin production, statin approval, statin testing, and stuff 0:18:23.080 --> 0:18:26.439 like that, which I will have some papers there if 0:18:26.480 --> 0:18:29.359 you want to dig more into that, Okay, But essentially, 0:18:29.640 --> 0:18:33.119 there were some early trials and animals that hit some hiccups, 0:18:33.200 --> 0:18:36.359 but then those were smoothed out. Trials and humans then 0:18:36.440 --> 0:18:40.240 went forward in the early nineteen eighties and results were striking. 0:18:40.960 --> 0:18:45.240 People with high cholesterol saw their LDL levels drop dramatically 0:18:45.400 --> 0:18:49.399 after taking the medication with few side effects. But did 0:18:49.640 --> 0:18:53.439 this drop translate to protection from cardiovascular disease? 0:18:53.840 --> 0:18:53.959 Right? 0:18:54.680 --> 0:18:57.639 You betcha yeah, you betcha yeah. 0:18:57.840 --> 0:18:58.080 Yeah. 0:18:58.680 --> 0:19:01.240 So there was one study sponsored by merk who was 0:19:01.240 --> 0:19:05.160 testing out there statin found a forty two percent decrease 0:19:05.280 --> 0:19:08.199 in death rate in those taking a statin. This is 0:19:08.240 --> 0:19:11.840 the second generation statin, simvastatin. 0:19:11.280 --> 0:19:14.920 Simvastatan still use it today, Yeah, wow Yeah. 0:19:15.040 --> 0:19:18.920 Statins look to be the next blockbuster drug, and soon 0:19:19.240 --> 0:19:22.960 every pharmaceutical company wanted in on the action, of course, 0:19:23.600 --> 0:19:26.359 and by the last year of the nineteen eighties, three 0:19:26.440 --> 0:19:29.560 statins were approved and available on the market. 0:19:29.880 --> 0:19:30.280 Wow. 0:19:31.119 --> 0:19:34.720 The following decade saw new statins and an expansion in 0:19:34.760 --> 0:19:38.400 their use, which allowed for large scale clinical studies, not 0:19:38.600 --> 0:19:42.160 just ones headed by pharmaceutical companies who were trying to 0:19:42.240 --> 0:19:46.320 get their drug approved. Also just can't believe how recent 0:19:46.840 --> 0:19:47.399 it all was. 0:19:47.600 --> 0:19:50.080 Me neither. I really did not realize that this was 0:19:50.119 --> 0:19:53.719 all in the last forty years since the nineteen eighties. 0:19:53.760 --> 0:19:54.880 That's really wild. 0:19:55.080 --> 0:19:57.800 It is wild, and I think it also is part 0:19:57.840 --> 0:20:00.000 of the reason why there's been such controversy. 0:20:00.760 --> 0:20:05.480 Hmmm. It's so interesting though, arin because there's so there's newer, newer, 0:20:05.600 --> 0:20:08.480 newer drugs that I feel like have way less controversy 0:20:08.560 --> 0:20:09.560 surrounding them. 0:20:09.640 --> 0:20:13.240 I know, And I'm just like, what, I there's a lot, 0:20:13.280 --> 0:20:14.960 there's a lot, and we're gonna we're gonna get into 0:20:14.960 --> 0:20:15.560 it in a second. 0:20:15.840 --> 0:20:16.240 Yeah. 0:20:16.240 --> 0:20:20.240 But yeah, But these studies, these large scale studies that 0:20:20.240 --> 0:20:23.560 were done not just by pharmaceutical industry, they conclusively and 0:20:23.680 --> 0:20:27.359 consistently showed that statins were life saving drugs and that 0:20:27.400 --> 0:20:31.200 they had earned their blockbuster status. Correct Across the board, 0:20:31.280 --> 0:20:34.040 statins led to a twenty five to thirty percent reduction 0:20:34.119 --> 0:20:38.560 in LDL coronary artery disease and death from cardiovascular disease. 0:20:39.560 --> 0:20:42.440 In the forty or so years since statins have been 0:20:42.480 --> 0:20:46.080 on the market, death from cardiovascular disease has dropped by 0:20:46.119 --> 0:20:50.159 over seventy five percent in many industrialized countries. Statins are 0:20:50.200 --> 0:20:53.640 a major tool in that fight, along with big advancements 0:20:53.640 --> 0:20:58.439 in medicine, lifestyle modifications, and diagnostics. But of course the 0:20:58.480 --> 0:21:03.560 story doesn't end here. The potential benefits of statins are enormous, 0:21:03.600 --> 0:21:08.080 both at a population and individual level, especially with cardiovascular 0:21:08.119 --> 0:21:10.880 disease being the leading cause of death in many countries. 0:21:11.840 --> 0:21:15.800 But increasingly the benefits of these drugs are not realized 0:21:15.840 --> 0:21:20.080 because people aren't taking statins when it's recommended that they do. 0:21:21.200 --> 0:21:22.600 Why is that? Why? 0:21:23.240 --> 0:21:23.480 Why? 0:21:24.119 --> 0:21:27.000 As it turns out, it's for many different reasons. A 0:21:27.000 --> 0:21:29.800 couple of recent papers looked into the issue and they 0:21:29.880 --> 0:21:33.240 presented some themes that they found in why people either 0:21:33.320 --> 0:21:38.479 refused or discontinued statins. There were, you know, practical and 0:21:38.600 --> 0:21:43.679 logistical considerations, so concern about taking multiple medications, polypharmacy burden, 0:21:44.280 --> 0:21:47.719 financial barriers, you know, having to drive to the clinic 0:21:47.800 --> 0:21:50.040 to get low cost statins, things like that. 0:21:50.040 --> 0:21:54.440 That's so annoying because they're all generic and not, especially 0:21:54.480 --> 0:21:56.560 in this country, be high costpits that they are, and. 0:21:56.560 --> 0:21:58.399 There should be you know, by mail et cetera. 0:21:58.600 --> 0:22:02.800 Yeah, yeah, yeah, pregnancy and breastfeeding is another sort of 0:22:02.840 --> 0:22:07.320 practical reason or preferring lifestyle modifications over a daily pill, 0:22:07.480 --> 0:22:09.000 like I'm not gonna be able to take a pill 0:22:09.000 --> 0:22:12.080 every single day, I'm gonna forget that. There were also 0:22:12.240 --> 0:22:17.560 preconceptions about side effects or impact on someone's identity, so 0:22:17.760 --> 0:22:20.920 people reported negative side effects or a fear of negative 0:22:20.920 --> 0:22:24.719 side effects, and others felt that taking statins was like 0:22:25.000 --> 0:22:28.080 giving up, that it signified sickness, and that they didn't 0:22:28.080 --> 0:22:29.800 want to be on a medication for the rest of 0:22:29.800 --> 0:22:31.560 their life. They didn't want to be dependent on this 0:22:31.680 --> 0:22:37.040 drug for health. And then there was another big reason 0:22:37.280 --> 0:22:40.880 or another big theme was mistrust in medicine and kind 0:22:40.880 --> 0:22:44.040 of a lack of understanding or belief in the drugs 0:22:44.160 --> 0:22:48.399 and how they worked, so some questioned their utility. Like 0:22:48.640 --> 0:22:51.040 I have high cholesterol. The doc says, I have high cholesterol, 0:22:51.119 --> 0:22:54.680 but I don't feel bad. Statins doesn't make me feel 0:22:54.680 --> 0:22:56.840 any different or it makes me feel worse. 0:22:57.160 --> 0:22:59.200 Right, I have this side effect that came from it, 0:22:59.320 --> 0:23:03.240 I think, And I didn't feel bad to begin with, right, exactly, 0:23:03.440 --> 0:23:05.200 why would I be on a medicine forever? 0:23:06.680 --> 0:23:10.960 People didn't also understand how statins lowered cholesterol, so it 0:23:11.000 --> 0:23:12.359 was just sort of like, well, I don't understand how 0:23:12.359 --> 0:23:14.879 they work, so I don't know that they do work. 0:23:15.520 --> 0:23:19.080 And many people also questioned the motives of doctors in 0:23:19.200 --> 0:23:22.680 prescribing the medication, like big Pharma has a hand in this, 0:23:23.080 --> 0:23:26.240 and they felt that over prescribing was an issue, especially 0:23:26.280 --> 0:23:29.639 with levels being revisited every so often and being like, 0:23:29.760 --> 0:23:32.520 now we recommend that you're you know, you didn't recommend 0:23:32.560 --> 0:23:34.360 me last year when my ELDALE. 0:23:33.960 --> 0:23:37.080 Was the same exactly. Now we need your LDAL to 0:23:37.080 --> 0:23:39.000 be less than seventy. Now we needed to be less 0:23:39.000 --> 0:23:42.359 than fifty five now, yeah, without a good explanation. They 0:23:42.480 --> 0:23:45.920 just updated the guidelines in March of this year, so 0:23:46.119 --> 0:23:47.440 they're changed yet again. 0:23:47.760 --> 0:23:50.399 Right, So there's this sort of fear of like diagnostic creep. 0:23:50.640 --> 0:23:53.920 Is that happening with cholesterol and statins or is there 0:23:54.000 --> 0:23:59.200 evidence to support this shifting of the levels and the recommendations. 0:24:00.040 --> 0:24:03.159 But often with all of these different reasons, it was 0:24:03.160 --> 0:24:06.240 a combination of things that led people to either refuse 0:24:06.280 --> 0:24:08.600 statins or stop taking them. 0:24:09.040 --> 0:24:11.280 Within two years, roughly. 0:24:11.000 --> 0:24:13.879 Forty percent of people who were taking them for primary 0:24:13.920 --> 0:24:16.760 prevention and twenty five percent of people on statins for 0:24:16.840 --> 0:24:21.240 secondary prevention end up stopping the medication. So to say 0:24:21.240 --> 0:24:24.720 that these negative attitudes towards statins are worrisome, I think 0:24:24.840 --> 0:24:29.439 is quite an understatement. It could have serious, even fatal consequences. 0:24:30.240 --> 0:24:33.080 So what do we do about it? The first step 0:24:33.200 --> 0:24:37.800 is understanding why, you know, where are these attitudes these 0:24:37.840 --> 0:24:42.080 beliefs coming from. Many of the reasons that people give 0:24:42.240 --> 0:24:46.239 for not taking or discontinuing statins can be attributed in 0:24:46.320 --> 0:24:52.040 part to misinformations or negative beliefs promoted across social media. 0:24:53.119 --> 0:24:55.800 When statins first came on the market in the late 0:24:55.880 --> 0:24:59.920 nineteen eighties, the cholesterol heart disease link had not yet 0:25:00.080 --> 0:25:03.280 been fully embraced by the general public, and in fact, 0:25:03.359 --> 0:25:07.120 there were some highly publicized front page stories written by 0:25:07.240 --> 0:25:13.840 vocal deniers controversy cells, consensus doesn't yes. And so all 0:25:13.840 --> 0:25:16.280 of a sudden, you go to the doctor. Your doctor 0:25:16.359 --> 0:25:18.480 is telling you should take this drug for your cholesterol. 0:25:18.480 --> 0:25:20.960 But just that morning you read how the cholesterol heart 0:25:20.960 --> 0:25:23.560 disease link is overblown so that big Pharma can rake 0:25:23.600 --> 0:25:25.200 in the dough and get people on meds for life. 0:25:25.920 --> 0:25:26.720 Why would you do this? 0:25:27.080 --> 0:25:32.240 Right? And it would take years after statins were introduced 0:25:32.280 --> 0:25:34.840 to put together those big data sets that show the 0:25:34.840 --> 0:25:37.760 life saving benefits of the drugs and the relatively low 0:25:37.880 --> 0:25:40.960 rate of side effects. And so doubt has really been 0:25:41.320 --> 0:25:45.320 sewn into statins from the very beginning, along with a 0:25:45.400 --> 0:25:48.600 mistrust in how the pharmaceutical industry is involved. 0:25:49.040 --> 0:25:50.240 And I get it, like. 0:25:50.280 --> 0:25:55.880 There is some truth to this involvement, especially early drug 0:25:55.920 --> 0:26:00.040 trials being designed by pharmaceutical companies. Many researchers in this 0:26:00.119 --> 0:26:03.800 area hold board positions or received funding from these companies 0:26:03.920 --> 0:26:06.680 or have a patent for these drugs, and they're trying, 0:26:06.760 --> 0:26:08.960 you know, like there is there are financial ties that 0:26:09.000 --> 0:26:10.520 are undeniable. 0:26:09.960 --> 0:26:12.400 One hundred percent, one hundred percent. And I will say 0:26:12.800 --> 0:26:16.400 like in today's day in age, not just with pharmaceutical companies, 0:26:16.440 --> 0:26:21.160 also with radiology companies and imaging companies and genetic testing companies, 0:26:21.200 --> 0:26:23.840 and so as our guidelines shift to incorporate more of these, 0:26:23.920 --> 0:26:28.919 like it is very valid to question these conflicts of interests, 0:26:28.920 --> 0:26:31.120 whether they are real or perceived, Like they. 0:26:30.960 --> 0:26:34.600 Matter, they matter, they do matter, And I think that 0:26:34.720 --> 0:26:37.640 this is, like you said, as these as these guidelines 0:26:37.640 --> 0:26:41.320 are shifting, there's these questions around like who, what's what's 0:26:41.359 --> 0:26:43.439 behind these guidelines, is there evidence for it? 0:26:43.520 --> 0:26:44.000 Et cetera. 0:26:45.200 --> 0:26:48.520 At the same time, decades of statin research. These drugs 0:26:48.520 --> 0:26:50.520 have been around for almost forty. 0:26:50.359 --> 0:26:51.240 Years forty years now. 0:26:51.320 --> 0:26:55.720 Yeah, decades of research have proven the value of statins, 0:26:55.760 --> 0:26:58.960 and that research is not solely conducted by industry, but 0:26:59.440 --> 0:27:02.679 large scale work being done across the globe, not just 0:27:02.720 --> 0:27:04.720 within pharmaceutical sectors in the United. 0:27:04.520 --> 0:27:06.080 States, but across the globe. 0:27:06.480 --> 0:27:09.560 And while yes, of course pharmaceutical companies love a drug 0:27:09.600 --> 0:27:11.960 that someone has to take for long periods of time, 0:27:12.480 --> 0:27:15.960 many statins today are available in a generic form, and 0:27:16.000 --> 0:27:18.840 so they're not as profitable as they once were. In 0:27:18.880 --> 0:27:21.919 any case, your primary care doc is not getting a 0:27:22.000 --> 0:27:25.080 kickback from prescribing these drugs. They simply don't want you 0:27:25.119 --> 0:27:26.280 to die from heart disease. 0:27:28.680 --> 0:27:30.439 It's so truely Arian, that's true. 0:27:30.480 --> 0:27:32.159 It's true. Okay. 0:27:32.200 --> 0:27:36.639 Another big reason that people cited was side effects, including 0:27:36.840 --> 0:27:40.240 or specifically muscle symptoms. This is one of the top 0:27:40.280 --> 0:27:43.879 reasons that people stop taking or never start taking statins. 0:27:44.520 --> 0:27:47.720 Side Effects are real and important to take seriously because 0:27:47.760 --> 0:27:51.399 they can truly impact quality of life. But the story 0:27:51.400 --> 0:27:54.680 of side effects when it comes to statins is complicated. 0:27:55.240 --> 0:27:56.560 Until two thousand. 0:27:56.200 --> 0:28:00.560 And one, there were very few reports of tolerability or 0:28:00.640 --> 0:28:04.000 safety concerns for people taking statins, but that year a 0:28:04.040 --> 0:28:09.440 statin seruvastatin, was removed from the market due to safety concerns, 0:28:09.560 --> 0:28:13.000 specifically for rahpdomiel issis, which occurred at a rate of 0:28:13.359 --> 0:28:15.960 zero point zero one percent in people. 0:28:15.720 --> 0:28:16.760 Taking it okay. 0:28:17.280 --> 0:28:20.880 Promptly after its removal from the market, all information sheets 0:28:20.880 --> 0:28:25.400 included warnings about all for all statins included warnings about 0:28:25.440 --> 0:28:29.760 muscle symptoms, and physicians counseled patients to report muscle aches 0:28:29.800 --> 0:28:34.240 as an early warning sign of rahpdomiel issis. This issue 0:28:34.240 --> 0:28:36.560 was highly publicized, as it should have been. You know, 0:28:36.640 --> 0:28:38.920 this is a potentially serious side effect, and so let's 0:28:39.040 --> 0:28:41.280 you know, make sure you look out for this. And 0:28:41.480 --> 0:28:45.160 many patients who felt muscle aches often would interpret them 0:28:45.200 --> 0:28:48.480 as myopathy or go to their doctor with concerns about myopathy. 0:28:48.960 --> 0:28:52.640 They would stop taking statins and their symptoms improved, which 0:28:52.800 --> 0:28:56.640 reinforced the belief that these statins might be dangerous, right, 0:28:56.920 --> 0:28:58.920 or the cause of that the cause of that? Right, 0:28:58.960 --> 0:29:03.160 And certainly these muscle symptoms were and are real, But 0:29:03.240 --> 0:29:07.320 there is also something called the nocibo effect that seems 0:29:07.360 --> 0:29:09.960 to be at play here, at least to some degree. 0:29:10.440 --> 0:29:13.680 So the nocebo effect is the opposite of the placebo effect. 0:29:14.000 --> 0:29:18.240 It's anticipation of negative symptoms that leads you to experience them. 0:29:19.160 --> 0:29:22.640 Studies on statins have shown that when both researcher and 0:29:22.880 --> 0:29:27.240 patient don't know whether someone is getting medication statin or placebo, 0:29:27.920 --> 0:29:32.440 both control and treatment groups experience similar rates of muscle aches, 0:29:33.040 --> 0:29:36.520 which suggests that it might not be the statins themselves 0:29:36.680 --> 0:29:39.560 directly responsible for those symptoms. 0:29:39.880 --> 0:29:41.680 Right, At least in all. 0:29:41.560 --> 0:29:45.760 Cases, the symptoms are absolutely real. The nocibo effect does 0:29:45.760 --> 0:29:48.440 not mean that it's all in your head. You're experiencing 0:29:48.600 --> 0:29:51.800 these symptoms. They just might not always be caused by 0:29:51.840 --> 0:29:52.840 the drug itself. 0:29:53.040 --> 0:29:55.720 Right. It's not like there's a direct mechanistic link between 0:29:55.800 --> 0:30:01.160 the drug that is directly causing that muscle symptom necessarily, right. 0:30:01.440 --> 0:30:03.040 But it could be. 0:30:03.200 --> 0:30:05.360 It could like, and so this is where it's really 0:30:05.400 --> 0:30:08.400 really tricky to tease apart both the patient and provider. 0:30:08.800 --> 0:30:11.360 And so it might be just like, feel like the 0:30:11.400 --> 0:30:13.680 easiest course to go, I'm just going to stop because 0:30:13.680 --> 0:30:15.320 I don't want to feel this way. I don't want to. 0:30:15.360 --> 0:30:17.760 I'm worried about this, and this is hurting my quality 0:30:17.800 --> 0:30:22.280 of life. I'm going to stop. Other research has also 0:30:22.320 --> 0:30:25.240 shown that people who are exposed to more negative stories 0:30:25.320 --> 0:30:29.280 surrounding statins and side effects are more likely to discontinue use. 0:30:30.040 --> 0:30:33.280 And I think that what's also at play here is 0:30:33.440 --> 0:30:35.160 when we kind of touched on this, is that we 0:30:35.240 --> 0:30:38.240 don't feel high cholesterol like, we don't feel any different 0:30:38.240 --> 0:30:41.960 when our cholesterol is low, but we do expect a 0:30:41.960 --> 0:30:45.000 lot of the time that the medications we take will 0:30:45.040 --> 0:30:48.280 make us feel different. We're supposed to feel better from 0:30:48.320 --> 0:30:52.440 these medications, supposed to feel something something yeah, yeah, And 0:30:52.520 --> 0:30:55.280 so it makes sense that if you read horror stories 0:30:55.280 --> 0:30:57.720 about side effects of statins that abound on the internet, 0:30:57.760 --> 0:31:01.200 you're predisposed to expect that those bad outcomes will happen 0:31:01.240 --> 0:31:04.640 to you. And what doesn't help this is that there 0:31:04.720 --> 0:31:08.480 is a vast amount of misinformation and disinformation about statins 0:31:08.480 --> 0:31:12.840 circulating on social media and generative AI. There's a motive 0:31:12.920 --> 0:31:16.200 for people to be spreading some of this misin disinformation. 0:31:16.960 --> 0:31:19.720 So in fact, there was a recent study that showed 0:31:19.720 --> 0:31:24.160 that many generative AI models, when fed prompts asking about statins, 0:31:24.280 --> 0:31:28.120 especially if those prompts were leading sort of like what 0:31:28.160 --> 0:31:29.160 can I take things? 0:31:29.560 --> 0:31:33.280 Isn't there some evidence of these side effects with statins 0:31:33.280 --> 0:31:35.080 like those kinds of questions. 0:31:34.760 --> 0:31:38.360 Yeah yeah, or like what should I take that's safer 0:31:38.400 --> 0:31:41.080 than statins? Like what natural product should I take that 0:31:41.120 --> 0:31:44.680 are that's safer than statins. But many of these models 0:31:44.760 --> 0:31:47.120 gave inappropriate and inaccurate answers. 0:31:47.320 --> 0:31:49.160 That doesn't surprise me at all, right. 0:31:49.240 --> 0:31:52.000 Right, the sheer amount of misinformation that's out there and 0:31:52.680 --> 0:31:56.600 just sort of the overall decline or disregard of expertise 0:31:56.640 --> 0:31:58.280 that's happening around the globe. 0:31:58.680 --> 0:31:59.520 Yeah there. 0:31:59.520 --> 0:32:02.080 And then there are the people who are very vocal 0:32:02.280 --> 0:32:04.800 in their opposition to statins, that at the same time 0:32:04.880 --> 0:32:07.800 are telling you don't go on statins, buy my red 0:32:07.880 --> 0:32:12.240 yeast rice supplement instead, or buy this diet book, or 0:32:12.640 --> 0:32:14.720 they're trying to make money off of you in some way, 0:32:14.880 --> 0:32:17.120 you know, subscribe to my sub stack that says, you know, 0:32:17.240 --> 0:32:20.480 day one diet with me, and right, I'll tell you 0:32:20.520 --> 0:32:24.400 throw away your statins, Yeah yeah, And that the thing 0:32:24.520 --> 0:32:27.000 is like I also understand why that's appealing when you've 0:32:27.040 --> 0:32:29.640 been dismissed by your physician, or your physician is saying 0:32:29.720 --> 0:32:32.600 it's not the statin causing this, just like that simply 0:32:32.640 --> 0:32:35.520 across the board, or if you can't even afford to 0:32:35.560 --> 0:32:39.520 go see a doctor, right, this this information is out there, 0:32:39.520 --> 0:32:43.880 and that is filling a hole that you want. 0:32:44.560 --> 0:32:46.920 And it feels like you're being taken seriously for the 0:32:46.960 --> 0:32:49.280 first time when you're like I went to my doctor 0:32:49.320 --> 0:32:51.400 with these concerns and you were totally dismissed or they 0:32:51.400 --> 0:32:54.840 were like, oh, you're fine, right, I'm not fine if 0:32:54.840 --> 0:32:56.520 I'm having symptoms, right. 0:32:56.480 --> 0:32:59.440 Yeah, And I mean again, like all of this, I 0:32:59.480 --> 0:33:03.560 think what it does is it speaks to a need 0:33:03.800 --> 0:33:07.480 to more closely examine the side effects that people report, 0:33:07.600 --> 0:33:09.840 not just muscle symptoms, but the other side effects that 0:33:09.840 --> 0:33:13.360 people report, and how best to address them, how best 0:33:13.400 --> 0:33:16.280 to measure them, How can we make it so that 0:33:16.360 --> 0:33:20.440 people can take drugs that will lower cholesterol and potentially 0:33:20.440 --> 0:33:24.400 save their lives. So again, what do we do about it? 0:33:24.720 --> 0:33:27.400 And I think that as a start, we can look 0:33:27.440 --> 0:33:31.320 at the reasons people take statons. So that same systematic 0:33:31.360 --> 0:33:35.040 review that I mentioned earlier also showed many people have 0:33:35.200 --> 0:33:39.960 positive sentiment towards these drugs. They trust their efficacy, like 0:33:40.400 --> 0:33:43.280 look how much my bad cholesterol dropped and my good 0:33:43.360 --> 0:33:48.320 cholesterol rose. They report that their health anxiety has eased 0:33:48.480 --> 0:33:51.960 thanks to the drugs, reporting an enhanced peace of mind, 0:33:52.840 --> 0:33:56.440 and they view them also as a way of taking 0:33:56.520 --> 0:34:02.080 control and ensuring a better, healthier future. Rebrand these drugs 0:34:02.120 --> 0:34:05.600 for what they are heart attack prevention, stroke prevention, a 0:34:05.640 --> 0:34:08.719 way to extend your life, your quality of life, and 0:34:08.800 --> 0:34:12.080 spend more time with the people you love, accomplishing all 0:34:12.120 --> 0:34:13.000 the things. 0:34:12.760 --> 0:34:13.520 You want to do. 0:34:14.400 --> 0:34:17.600 These drugs might not make you feel any better instantaneously, 0:34:17.920 --> 0:34:20.640 but they will make it more likely that you're around 0:34:20.680 --> 0:34:24.640 to feel and do things ten years from now. Having 0:34:24.719 --> 0:34:27.480 high cholesterol it doesn't mean that you have failed. It 0:34:27.520 --> 0:34:30.279 should not be seen as shameful, as something that you 0:34:30.320 --> 0:34:34.839 should hide or feel embarrassed by, and taking these medications 0:34:34.840 --> 0:34:37.480 should make you feel like you're taking agency over your 0:34:37.480 --> 0:34:41.240 own life. Prevention is always harder, especially when the threat 0:34:41.440 --> 0:34:43.920 like a heart attack, doesn't seem imminent or is so 0:34:44.040 --> 0:34:45.960 scary that you're like, I have to think that this 0:34:46.000 --> 0:34:47.040 won't happen to me. 0:34:47.880 --> 0:34:50.040 I can't put my mind in that place. 0:34:50.320 --> 0:34:54.160 Yes, but that denial it really does not serve us well. 0:34:54.440 --> 0:34:56.319 And so with that eron, I'm going to turn it 0:34:56.360 --> 0:34:59.120 over to you to tell us about how statins actually 0:34:59.160 --> 0:35:02.640 work and where things stand with cardiovascular disease around the 0:35:02.680 --> 0:35:03.520 globe today. 0:35:04.000 --> 0:35:26.080 I would love to so knowing that statins have made 0:35:26.120 --> 0:35:29.160 such a huge impact, or have the potential at least 0:35:29.200 --> 0:35:32.239 to make such a huge impact on disease, I think 0:35:32.280 --> 0:35:34.120 we first need to understand a little bit more about 0:35:34.120 --> 0:35:37.560 how they work. So I want to go through not 0:35:37.680 --> 0:35:42.200 just statins, but the strategies overall that we use today 0:35:42.320 --> 0:35:49.000 to lower LDL cholesterol, specifically how these strategies work, and 0:35:49.040 --> 0:35:51.560 then I want to wrap up by giving us all 0:35:51.600 --> 0:35:55.880 like a reminder of why lowering cholesterol is so important, 0:35:55.920 --> 0:36:00.960 by looking at athrosclerotic heart disease kind of across the globe. Okay, 0:36:02.239 --> 0:36:04.000 And so the first thing to know is that while 0:36:04.040 --> 0:36:07.480 statins are because of how long they've been around and 0:36:07.560 --> 0:36:11.160 because of how strong the evidence is that they are 0:36:11.360 --> 0:36:15.400 extremely effective not just at lowering that cholesterol, but actually 0:36:15.480 --> 0:36:19.879 at preventing heart attack, stroke and death. They are a 0:36:19.920 --> 0:36:24.920 mainstay of therapy today for cholesterol management, but they are 0:36:24.960 --> 0:36:28.520 not the only thing that we have. And the first 0:36:28.600 --> 0:36:32.480 thing that is always recommended across the board is diet 0:36:32.520 --> 0:36:36.399 and lifestyle changes. And the thing is that we do 0:36:36.520 --> 0:36:40.719 have really decent data as far as nutrition data goes, 0:36:40.760 --> 0:36:44.600 which we all know is limited. Yep, we do have 0:36:44.680 --> 0:36:48.400 decent data that lifestyle changes can work for a lot 0:36:48.440 --> 0:36:52.160 of people. But the problem is that we also know 0:36:52.520 --> 0:36:58.200 that your total cholesterol and your LDL cholesterol, so the 0:36:58.560 --> 0:37:04.480 packages of LDL cholesterol are not entirely driven by your diet. 0:37:04.960 --> 0:37:08.640 They're not entirely driven by how much exercise you're getting, right. 0:37:09.040 --> 0:37:12.600 There are a lot of different things that go into 0:37:12.760 --> 0:37:16.120 determining what your cholesterol levels are and whether they are 0:37:16.200 --> 0:37:18.839 high or whether they are low. And one of the 0:37:19.000 --> 0:37:23.440 big things is our genetics. You talked in last week's 0:37:23.440 --> 0:37:28.399 episode AARIN about familial hypercholesterolemia. This is one or really 0:37:28.440 --> 0:37:33.319 kind of like one group of disorders that can seriously 0:37:33.400 --> 0:37:39.520 contribute to elevated cholesterol, especially LDL cholesterol. But it's not 0:37:39.600 --> 0:37:42.160 the only one. There are a whole bunch of other 0:37:42.400 --> 0:37:46.759 genetic contributions, whether that's multiple genes or things that we 0:37:46.800 --> 0:37:49.359 don't even know yet, right, Genes that we haven't even 0:37:49.400 --> 0:37:53.600 discovered yet that are associated with the ratios and amounts 0:37:53.600 --> 0:37:57.200 of cholesterol, whether that's because these genes affect how we 0:37:57.320 --> 0:38:02.080 recycle cholesterol, whether they affect how much cholesterol we produce 0:38:02.120 --> 0:38:06.680 in our liver, or whether like in familial hypercholesterolemia, they 0:38:06.680 --> 0:38:10.080 affect our LDL receptors and how good our cells are 0:38:10.200 --> 0:38:13.439 at taking that cholesterol out of our bloodstream right, right, 0:38:14.239 --> 0:38:16.040 So all of these things are going to play a 0:38:16.120 --> 0:38:19.880 role as well as our dietary factors and our lifestyle factors, 0:38:19.880 --> 0:38:23.240 and so that is usually the first thing that any 0:38:23.360 --> 0:38:26.920 physician is going to recommend if someone's cholesterol is elevated, 0:38:27.239 --> 0:38:31.960 is can we bring this down by reducing or stopping 0:38:32.000 --> 0:38:34.600 smoking if you smoke, because that has a huge effect 0:38:34.840 --> 0:38:37.040 Lowering the amount of alcohol that you drink, which is 0:38:37.080 --> 0:38:40.479 going to help to lower your cholesterol levels. Switching out 0:38:40.640 --> 0:38:45.200 saturated fats in your diet for unsaturated fats, right, switching 0:38:45.200 --> 0:38:49.040 out animal products for plant products. These are the kinds 0:38:49.080 --> 0:38:53.200 of dietary changes that we have good data to say 0:38:53.239 --> 0:38:57.759 that not only do they reduce your cholesterol levels, but 0:38:57.800 --> 0:39:01.960 they also can actually prevent cardiovascular disease. We have that data, 0:39:02.040 --> 0:39:07.120 it exists, but for many people that isn't sufficient, and 0:39:07.160 --> 0:39:11.799 so that is when it is recommended that medication is 0:39:11.800 --> 0:39:15.320 actually used, right, whether it's because somebody can't or doesn't 0:39:15.360 --> 0:39:18.840 want to change their diet or exercise, or they can't 0:39:18.880 --> 0:39:22.000 increase physical activity, or they are literally already doing the 0:39:22.000 --> 0:39:26.280 most and it's still not enough. And that happens so 0:39:26.280 --> 0:39:27.600 so so often. 0:39:27.400 --> 0:39:29.440 Right, And I think it's like, this is where I 0:39:29.480 --> 0:39:32.480 feel like it can feel like I have failed or 0:39:33.000 --> 0:39:35.520 I thought I was trying my best to do all 0:39:35.560 --> 0:39:37.760 these things and still it's not working. 0:39:37.880 --> 0:39:38.440 And it's like. 0:39:38.440 --> 0:39:42.120 That that's okay, Like this is not your no, you're 0:39:42.160 --> 0:39:43.520 not a failure of No. 0:39:43.840 --> 0:39:46.680 Yeah, no, it's that's so true, Aaron, Like I see 0:39:46.680 --> 0:39:48.719 people in clinic all the time that this happens too, 0:39:48.840 --> 0:39:51.719 and I just say, blame your parents, like it's probably 0:39:51.800 --> 0:39:57.200 your genes. Okay. So let's then talk about what are 0:39:57.440 --> 0:39:59.640 some of the big medicines that we use and how 0:39:59.719 --> 0:40:04.759 do they actually work. Why are they working? Yes, yes, statins. 0:40:05.840 --> 0:40:05.960 So. 0:40:06.239 --> 0:40:11.440 Statins block an enzyme in our liver that's called hmg 0:40:11.680 --> 0:40:16.240 CoA reductase. The cliff Notes version is that this particular enzyme, 0:40:16.480 --> 0:40:22.760 hmg CoA reductase, this one is the rate limiting step 0:40:23.160 --> 0:40:27.440 in cholesterol synthesis in your liver, so that enzyme is 0:40:27.520 --> 0:40:30.400 necessary in our liver for our liver to make cholesterol. 0:40:30.400 --> 0:40:33.520 And remember, our liver is making over fifty percent of 0:40:33.560 --> 0:40:35.360 the cholesterol floating around in our body. 0:40:35.440 --> 0:40:38.560 Right, so you have if you have more hmg CoA reductase, 0:40:38.640 --> 0:40:40.920 then you have more cholesterol photogram in your body. If 0:40:40.960 --> 0:40:45.000 you reduce that reductase that enzyme, then you have less. 0:40:45.520 --> 0:40:48.560 And Aaron, it goes even further than that, Okay, because 0:40:48.560 --> 0:40:51.880 what happens is that by blocking this enzyme in particular, 0:40:52.120 --> 0:40:54.920 because it is the rate limiting step, meaning it's like 0:40:54.960 --> 0:40:57.399 the slowest one in the daisy chain right when you're 0:40:57.480 --> 0:41:01.960 moving stuff into our house, we dramatically reduce, not just 0:41:02.000 --> 0:41:04.719 like a little bit do we reduce how much cholesterol 0:41:04.760 --> 0:41:07.760 your liver's making. You're dramatically reducing, like putting a huge 0:41:07.760 --> 0:41:11.600 break on how much cholesterol your liver can make. And 0:41:12.120 --> 0:41:17.480 because all of our cells still need cholesterol, our cells 0:41:17.680 --> 0:41:21.440 have to get better at taking cholesterol out of our bloodstream, 0:41:21.680 --> 0:41:25.840 so they actually up regulate those LDL receptors, those velcro, 0:41:25.920 --> 0:41:28.960 sticky hands on the surface of our cells that capture 0:41:29.080 --> 0:41:32.279 our LDL cholesterol floating around in our bloodstream. So it's 0:41:32.320 --> 0:41:35.000 not just that, oh, we're not making as much cholesterol, 0:41:35.040 --> 0:41:37.560 it's that we're not making as much cholesterol and our 0:41:37.600 --> 0:41:41.040 body cells still need cholesterol, so they start vacuuming it 0:41:41.160 --> 0:41:43.200 out of our bloodstream at really high rates. 0:41:44.120 --> 0:41:45.880 Beautiful. Isn't that cool? 0:41:46.200 --> 0:41:46.319 Oh? 0:41:46.400 --> 0:41:47.759 Yeah, I love that. 0:41:48.160 --> 0:41:51.120 There's also some interesting evidence that statin's also might have 0:41:51.239 --> 0:41:54.280 a little bit of like an anti inflammatory effect as well. 0:41:54.680 --> 0:41:56.160 Yeah, and we talked. 0:41:55.840 --> 0:42:00.239 In last week's episode about how important inflammation is in 0:42:00.320 --> 0:42:03.680 the process of atherosclerosis or in the process of that 0:42:03.760 --> 0:42:08.279 cholesterol actually forming a plaque in your bloodstream. Inflammation is 0:42:08.320 --> 0:42:10.479 an integral part of that, and so there's some thought 0:42:10.520 --> 0:42:13.680 that there's also an anti inflammatory effect of statins, though 0:42:13.680 --> 0:42:17.600 we don't fully understand that mechanism there. So that's how 0:42:17.600 --> 0:42:22.480 statins work, and they're incredibly effective erin. There was a 0:42:22.520 --> 0:42:26.880 meta analysis from twenty sixteen that was really interesting, So 0:42:26.880 --> 0:42:29.239 it's kind of old now, but it looked at over 0:42:29.280 --> 0:42:32.000 fifty different studies that looked at all the different possible 0:42:32.000 --> 0:42:35.040 interventions that we had at that time and all of 0:42:35.160 --> 0:42:40.480 the randomized control trials of those different interventions and the 0:42:40.560 --> 0:42:45.000 effect of lowering LDL cholesterol on cardiovascular disease risk by 0:42:45.040 --> 0:42:51.120 these different interventions. Okay, we had twenty five trials on statins, 0:42:52.239 --> 0:42:55.840 twenty five of them compared to only four diet trials 0:42:56.239 --> 0:42:59.640 compared to only two at the time on PCSK nine 0:42:59.680 --> 0:43:01.480 in hibit which I'll get to in a second, right 0:43:01.760 --> 0:43:04.439 one on a zmib, which is another medicine that we use. 0:43:04.800 --> 0:43:07.040 And so what that means is not only do we 0:43:07.120 --> 0:43:10.120 have so much data on their effect, it also means 0:43:10.160 --> 0:43:14.360 that our confidence intervals on just exactly how effective they 0:43:14.400 --> 0:43:18.680 are are really narrow for statins. So we know, like 0:43:18.840 --> 0:43:22.920 without a doubt that statins are extremely effective at lowering 0:43:23.000 --> 0:43:27.320 our LDL cholesterol and at reducing the risk of adverse 0:43:27.360 --> 0:43:28.440 cardiovascular events. 0:43:28.880 --> 0:43:31.279 Period is that what is what did that study show? 0:43:31.360 --> 0:43:33.960 The meta analysis show in terms of like that by 0:43:34.000 --> 0:43:35.520 the numbers impact. 0:43:35.320 --> 0:43:38.520 So by the numbers, statins are the most consistent. Diet 0:43:38.640 --> 0:43:41.799 is A has a slightly less effect but still a 0:43:41.840 --> 0:43:45.200 significant effect. PCSK nines, which I'll get to in a second, 0:43:45.480 --> 0:43:48.799 have the greatest effect. They lower LDL cholesterol the most 0:43:48.920 --> 0:43:51.160 and they reduce your risk the most. But the confidence 0:43:51.200 --> 0:43:53.480 intervals are super wide because at least at that time, 0:43:53.480 --> 0:43:56.759 we just didn't have as much data on them, right, right, Yeah, 0:43:56.760 --> 0:43:58.600 and then the other ones are in between. But statins 0:43:58.600 --> 0:44:01.200 are like like pound I guess, I don't know if 0:44:01.239 --> 0:44:04.040 that's right, but like incredibly effective and like just so 0:44:04.200 --> 0:44:05.719 much good data to support them. 0:44:06.080 --> 0:44:08.839 We're really dialed in on how statins work and how 0:44:08.880 --> 0:44:09.479 well they work. 0:44:09.920 --> 0:44:10.319 Are there? 0:44:10.560 --> 0:44:13.480 What are the differences between different types of statins? 0:44:13.880 --> 0:44:17.120 Great question, So different types of statins. A lot of 0:44:17.120 --> 0:44:20.640 the difference is in their potency. So some statins can 0:44:20.800 --> 0:44:24.279 lower your LDL cholesterol to a much greater degree than 0:44:24.320 --> 0:44:28.520 other statins, the exact of like why, I don't know, okay, 0:44:29.440 --> 0:44:32.160 but that means that we have statins that vary in 0:44:32.239 --> 0:44:36.040 what we call their intensity, And by intensity we mean 0:44:36.160 --> 0:44:41.160 how much, by what percentage are we lowering your LDL cholesterol. 0:44:41.400 --> 0:44:43.160 So if I can give you a medicine that's going 0:44:43.239 --> 0:44:46.560 to lower your LDL cholesterol by at least fifty percent, 0:44:47.360 --> 0:44:51.239 that's considered a high intensity statin regimen. And if it's 0:44:51.239 --> 0:44:53.959 by less than thirty percent, then that's considered a low 0:44:54.040 --> 0:44:59.120 intensity regimen. And then there's intermediate in between. Okay, okay, yeah, moderate. 0:45:00.239 --> 0:45:03.919 There's also differences in like some of them are more lipophilic, 0:45:04.080 --> 0:45:06.600 so they're more like fats, and some of them are 0:45:06.600 --> 0:45:09.880 more hydrophilic, so they're more like They act more like 0:45:09.920 --> 0:45:13.560 proteins in that they're more like soluble in water, and 0:45:13.640 --> 0:45:15.920 so that might differ in how much they build up 0:45:15.920 --> 0:45:18.920 in different tissues in your body. But there's not great 0:45:19.000 --> 0:45:22.160 data that says that one is more or less likely 0:45:22.200 --> 0:45:24.120 to cause side effects than the other. And that's the 0:45:24.120 --> 0:45:26.680 next thing I want to briefly talk about because it's 0:45:26.719 --> 0:45:30.240 an important part of the statin story and you mentioned 0:45:30.239 --> 0:45:33.319 it as well Erin it is not the case that 0:45:33.360 --> 0:45:39.239 side effects don't exist. Any medication, any therapy really has 0:45:39.239 --> 0:45:42.960 the potential to cause side effects. And like you mentioned, Aaron, 0:45:43.160 --> 0:45:47.280 the most cited side effect that causes people to stop 0:45:47.400 --> 0:45:51.440 taking a statin medication is muscle symptoms, and that's a 0:45:51.480 --> 0:45:56.040 really general term. It's often muscle pain or muscle aches, 0:45:56.120 --> 0:46:00.239 or sometimes muscle weakness. Now there's also other things like 0:46:00.239 --> 0:46:04.799 gastro intestinal side effects or liver enzymes can increase, which 0:46:04.840 --> 0:46:08.040 is usually transient and can be completely reversed either by 0:46:08.040 --> 0:46:10.400 going down on the dose or stopping the statin. But 0:46:10.520 --> 0:46:15.040 muscle effects are like the big one, right and there 0:46:15.120 --> 0:46:19.000 was a recent meta analysis that looked at data from 0:46:19.080 --> 0:46:22.360 randomized control trials from over one hundred and fifty thousand 0:46:22.360 --> 0:46:27.600 people and twenty three different studies that were comparing either 0:46:27.880 --> 0:46:31.720 statins versus place EBO or different intensity as a statin, 0:46:31.840 --> 0:46:35.640 so that high intensity versus low intensity therapy. And what 0:46:35.680 --> 0:46:39.400 they found is not that muscle symptoms were never reported 0:46:39.440 --> 0:46:43.920 by any means, but that by comparing all these different regimens, 0:46:44.080 --> 0:46:48.160 what they estimated was that less than ten percent of 0:46:48.239 --> 0:46:52.080 all of the reports of muscle symptoms could actually be 0:46:52.239 --> 0:46:55.239 directly attributed to statins themselves. 0:46:55.520 --> 0:46:57.680 Does that make sense, I think so. 0:46:57.680 --> 0:47:00.680 So the it's not talking about the rate of side 0:47:00.680 --> 0:47:05.320 effects that happen, No, how much of those side effects 0:47:05.360 --> 0:47:09.920 are statin's directly responsible for cause exactly? And is this 0:47:10.080 --> 0:47:12.359 based on like do we understand mechanism? 0:47:12.600 --> 0:47:13.760 Oh, such a good question. 0:47:13.800 --> 0:47:14.240 We don't. 0:47:14.680 --> 0:47:17.920 We don't. Because the vast majority of these, even the 0:47:17.960 --> 0:47:21.840 side effects that could be attributed to statins are considered mild. 0:47:22.200 --> 0:47:25.080 A lot of people actually will continue their statin and 0:47:25.360 --> 0:47:28.160 the amount of people who report symptoms after the first 0:47:28.239 --> 0:47:30.880 year actually goes down. So it's usually in that first 0:47:30.920 --> 0:47:33.839 year of therapy. Realistically, it's usually within the first few 0:47:33.880 --> 0:47:36.719 weeks or months of starting a statin medicine that people 0:47:36.719 --> 0:47:39.280 are more likely to have effects directly related to the statin. 0:47:40.560 --> 0:47:43.400 But no, we don't understand exactly the mechanism. But most 0:47:43.440 --> 0:47:47.200 of them are mild and they do not result in 0:47:47.440 --> 0:47:52.480 actual damage to the muscle, tissue or myopathy. Now that 0:47:52.520 --> 0:47:57.480 does not mean that they can't ever, Right, there are 0:47:57.600 --> 0:48:01.600 more serious events like rhabdomyolysis, and that is estimated to 0:48:01.640 --> 0:48:07.040 occur about four excess cases per ten thousand people if 0:48:07.080 --> 0:48:09.560 you're on a high intensity statin. Does that mean there's 0:48:09.600 --> 0:48:12.120 only four But like some people get rabdo that has 0:48:12.160 --> 0:48:15.080 nothing to do with statins, So statins will call its 0:48:15.200 --> 0:48:18.400 four excess cases for every ten thousand people on a 0:48:18.480 --> 0:48:19.680 high intensity statin. 0:48:19.920 --> 0:48:22.200 Is it more common? Okay you were about to say yes. 0:48:22.400 --> 0:48:24.840 Yeah, and one per ten thousand on less intensive So 0:48:24.880 --> 0:48:28.080 it does go up, like the chances of side effects 0:48:28.120 --> 0:48:30.879 and the chances of more severe side effects go up 0:48:30.920 --> 0:48:35.000 with intensity. So sometimes just going down from a high 0:48:35.080 --> 0:48:38.239 intensity regimen to a lower intensity regimen takes away side 0:48:38.239 --> 0:48:40.480 effects entirely for people, and that's enough and then you're 0:48:40.520 --> 0:48:43.239 still getting some benefit, just maybe not quite as much 0:48:43.280 --> 0:48:45.120 as you were on a high intensity regimen. 0:48:45.560 --> 0:48:49.080 Okay, question about that meta analysis. You said that ten 0:48:49.120 --> 0:48:53.799 percent of the side effects experience are directly attributable to statins. 0:48:54.120 --> 0:48:56.920 What is the ninety percent? Where does that get attributed to? 0:48:57.200 --> 0:48:59.480 I don't know, I don't We don't have an answer 0:48:59.480 --> 0:48:59.759 to that. 0:49:00.320 --> 0:49:01.920 Just the hyper didn't suggest anything. 0:49:02.040 --> 0:49:04.200 No any answers, Okay, no, I mean some of it. 0:49:04.360 --> 0:49:07.120 They're like, is it just aging, is it just no 0:49:07.239 --> 0:49:10.600 stibo effect? Is it like a bunch of different possible things, 0:49:11.320 --> 0:49:12.920 but not like a clear answer. No. 0:49:13.719 --> 0:49:16.080 And so this was like by looking at people who 0:49:16.160 --> 0:49:19.799 are on placebo are still experiencing these side effects and 0:49:19.840 --> 0:49:21.400 we don't know what's causing that, Okay. 0:49:21.239 --> 0:49:24.200 Right, So then you're looking at like how many excess cases, 0:49:24.520 --> 0:49:28.720 how many excess reports will you get? It was estimated 0:49:28.760 --> 0:49:31.920 like eleven reports of muscle pain or weakness per one 0:49:31.960 --> 0:49:36.640 thousand people on statins in that first year were from statins. Okay, 0:49:37.280 --> 0:49:38.680 eleven per one thousand. 0:49:38.800 --> 0:49:40.920 Right, So it's tricky. 0:49:41.000 --> 0:49:44.000 It's really really really tricky because it's not that these 0:49:44.480 --> 0:49:47.960 symptoms are not real, right, And and if you are 0:49:48.080 --> 0:49:51.759 one of those people who has that severe side effect, right, 0:49:51.840 --> 0:49:54.920 one of four per ten thousand. That's a very real 0:49:55.200 --> 0:49:59.040 effect for you. And so it is always a tricky 0:49:59.080 --> 0:50:03.120 thing to balance because when we are talking about treating 0:50:03.280 --> 0:50:07.000 and preventing, especially when we're talking about preventing cardiovascular disease, 0:50:08.040 --> 0:50:12.200 we are talking both about population level reductions and risk, 0:50:12.480 --> 0:50:16.239 and we're also talking about an individual risk benefit calculation, 0:50:16.640 --> 0:50:20.480 right and so, and those are not the same calculations 0:50:20.480 --> 0:50:22.800 on a population scale versus on an individual scale. 0:50:22.960 --> 0:50:24.160 Yeah, and yeah. 0:50:24.200 --> 0:50:27.200 It doesn't help when people's symptoms are completely ignored, or 0:50:27.239 --> 0:50:30.719 when they're told oh, it's absolutely not from this, or 0:50:30.760 --> 0:50:34.120 when they're told from wellness influencers online that this medication 0:50:34.200 --> 0:50:37.759 that they've been on safely for ten years is now 0:50:37.840 --> 0:50:41.120 causing the symptoms that they're having, right yeah, yeah, yeah, yeah, 0:50:41.120 --> 0:50:42.240 which I see all the time. 0:50:42.360 --> 0:50:45.160 I mean I think that what is a real challenge too, 0:50:45.360 --> 0:50:48.279 is like how do you balance saying Okay, these are 0:50:48.320 --> 0:50:50.840 real symptoms, you are experiencing this, this is very real 0:50:51.640 --> 0:50:53.840 is and deciding is this caused by the statina, is 0:50:53.840 --> 0:50:56.360 this not caused by the statin? Are you going to 0:50:56.400 --> 0:50:59.960 be someone who is the point zero zero one percent 0:51:00.360 --> 0:51:02.719 are right? And then it's like what even if these 0:51:03.000 --> 0:51:06.919 side effects are not directly caused by the statin, they're 0:51:06.960 --> 0:51:10.839 still impeding your ability to say, exercise or something like that. 0:51:10.880 --> 0:51:13.200 And so it's like, gona be helpful for your health, right, 0:51:13.840 --> 0:51:16.680 it's a mess. I'm very curious to hear suggestions on 0:51:16.760 --> 0:51:18.480 how out of a question. 0:51:18.680 --> 0:51:20.880 I mean, I don't know, Like I really think that 0:51:20.920 --> 0:51:22.960 what it always has to come down to is a 0:51:23.000 --> 0:51:27.279 good relationship with a physician or provider that you trust, right, 0:51:27.719 --> 0:51:31.439 who knows you, who you know, who can explain these 0:51:31.440 --> 0:51:34.200 things to you. And like, it's why I don't think 0:51:34.239 --> 0:51:36.920 AI can take over for all doctors Aaron. But maybe 0:51:36.920 --> 0:51:37.800 that's my bias. 0:51:37.880 --> 0:51:40.600 Well it's not, but I think it is the way 0:51:40.760 --> 0:51:44.680 that medicine is going, and like the and has been 0:51:44.760 --> 0:51:45.480 trending in. 0:51:45.440 --> 0:51:47.480 The last twenty years, more. 0:51:47.320 --> 0:51:53.000 Expensive, shorter visits, yep, more video visits that don't always 0:51:53.040 --> 0:51:56.919 necessarily feel like you're having a connection with someone, right, 0:51:56.960 --> 0:51:59.160 it all is just standing in the way of forming 0:51:59.160 --> 0:52:00.640 these relationships. 0:52:00.239 --> 0:52:02.600 I know, because they're the most important thing in my 0:52:03.520 --> 0:52:08.680 highly biased opinion. Ah okay, but we have more options too. 0:52:08.840 --> 0:52:11.359 Some people are gonna have side effects from statins or 0:52:11.400 --> 0:52:13.920 they're just like no, I will not take a statin. Cool, 0:52:14.120 --> 0:52:17.120 don't worry. We have other options now, and I'm not 0:52:17.120 --> 0:52:18.640 going to go through every single one, but I'm going 0:52:18.719 --> 0:52:20.799 to call out two that are probably like the two 0:52:20.840 --> 0:52:24.879 biggest groups that we use. One is called zetimibe, and 0:52:25.080 --> 0:52:29.640 this is a drug that blocks a protein that's in 0:52:29.760 --> 0:52:33.000 the cell membranes of our guts and our bile ducts. 0:52:33.320 --> 0:52:36.279 So what this does is it blocks the amount of 0:52:36.360 --> 0:52:40.880 cholesterol that we are absorbing and reabsorbing. So this one, 0:52:40.920 --> 0:52:43.840 it doesn't have as huge of an effect by any means, 0:52:43.840 --> 0:52:47.000 but it can still lower cholesterol, often by like ten percent. 0:52:47.080 --> 0:52:50.479 We're talking LDL cholesterol. It can lower you. So that's 0:52:50.560 --> 0:52:53.399 not nothing to shake a stick at. So now let 0:52:53.480 --> 0:52:56.920 me talk about the one that people are so excited about. 0:52:56.920 --> 0:52:59.920 And then I said multiple times that is a non 0:53:00.080 --> 0:53:04.399 since we're called PCSK nine inhibitor skin. Okay. PCSK nine 0:53:04.520 --> 0:53:06.560 is the shorthand name for a protein that I'm not 0:53:06.560 --> 0:53:08.400 going to tell you the name of because I don't 0:53:08.640 --> 0:53:10.880 know it. It's too long. But this is a protein 0:53:10.920 --> 0:53:15.360 that our liver makes. It's really interesting. Its job this 0:53:15.520 --> 0:53:22.840 protein is to degrade break down LDL receptor proteins. Okay, 0:53:23.560 --> 0:53:26.799 so this protein is kind of like an anti recycler 0:53:27.719 --> 0:53:32.400 of this protein, of this receptor who usually collects the 0:53:32.600 --> 0:53:37.160 LDL in our bloodstream. Okay, yeah, Why does this protein 0:53:37.239 --> 0:53:39.880 do this, I don't know right now, but that is 0:53:39.880 --> 0:53:44.640 what it does. So if you can block this enzyme, 0:53:45.200 --> 0:53:51.560 this protein, then you will have more LDL receptors available 0:53:51.840 --> 0:53:55.720 to be reused and recycled to be collecting our LDL 0:53:55.840 --> 0:53:59.360 cholesterol in our bloodstream. 0:53:59.680 --> 0:54:04.360 So this is like a velcro glove thief, this this protein. 0:54:04.239 --> 0:54:08.160 The protein. Yeah, PCSK nine exactly, it's a velcro glove thief. 0:54:08.480 --> 0:54:12.560 Then the velco gloves are numerous to catch all those 0:54:12.719 --> 0:54:14.720 tennis balls of LDL. 0:54:15.200 --> 0:54:16.600 I really like this analogy, by the. 0:54:16.560 --> 0:54:19.560 Way, it's a really good analogy. I'm yeah, thanks. 0:54:19.600 --> 0:54:21.360 You know, I don't always come up with good ones. 0:54:21.200 --> 0:54:22.960 So I mean the best I get it was Bill Buckner. 0:54:23.040 --> 0:54:24.360 So I've really. 0:54:24.160 --> 0:54:28.800 Enjoyed that so much more than I can say. Yeah, 0:54:28.840 --> 0:54:32.239 So that is how PCSK nine inhibitors work. The main group, Like, 0:54:32.280 --> 0:54:34.200 there's a couple different medicines that we use that are 0:54:34.280 --> 0:54:39.040 mostly monoclonal antibodies. They're really interesting because a lot of times, 0:54:39.040 --> 0:54:40.880 Like they're not a pill that you have to take 0:54:40.920 --> 0:54:44.279 every day. It's like an injectable medicine that you take 0:54:44.280 --> 0:54:46.839 every week or two weeks, depending on the medicine. There's 0:54:46.880 --> 0:54:51.719 also something called in chlyserin, which is a small interfering 0:54:51.920 --> 0:54:59.520 RNA molecule okay, that binds to this protein's PCSK nine's 0:54:59.840 --> 0:55:04.240 m and degrades it. So it's also affecting that same system, 0:55:04.560 --> 0:55:09.040 it's just not blocking the receptor itself. Isn't that so cool? 0:55:09.400 --> 0:55:10.040 Wow? 0:55:10.160 --> 0:55:12.720 And the data on all of these medicines that affect 0:55:12.760 --> 0:55:16.560 PCSK nine it is incredibly strong. So we talked about 0:55:16.600 --> 0:55:19.040 that that meta analysis from ten years ago or so. 0:55:19.360 --> 0:55:26.040 PCSK nine inhibitors reduce your LDL drastically and can drastically 0:55:26.080 --> 0:55:30.359 also reduce cardiovascular events, especially in people who are very 0:55:30.440 --> 0:55:33.400 high risk, meaning people that we are doing secondary prevention 0:55:34.040 --> 0:55:37.439 who already have you know, cardiovascular dues, who have maybe 0:55:37.440 --> 0:55:39.279 already had a heart attack or a stroke and we 0:55:39.440 --> 0:55:41.960 really need to lower that cholesterol, or people who are 0:55:42.000 --> 0:55:46.319 just very high risk. Right, So in those populations is 0:55:46.320 --> 0:55:50.080 mostly where it's been studied, and so cardiologists love this medicine. 0:55:50.800 --> 0:55:55.759 The biggest issues are as with all new drugs, especially 0:55:55.800 --> 0:56:01.080 ones that are fancy things like siRNA and monoclonal antibodies. 0:56:01.120 --> 0:56:05.960 They are expensive as heck, especially in this country. We 0:56:06.040 --> 0:56:09.560 also just don't have nearly as much data on them 0:56:09.600 --> 0:56:12.200 as we do for statins, so the error bars on 0:56:12.239 --> 0:56:16.160 their benefit is still messier, even though they still have 0:56:16.200 --> 0:56:17.040 a really good effect. 0:56:18.000 --> 0:56:20.560 Do we have information about side effects? 0:56:20.960 --> 0:56:22.879 It's a great question. I should have looked into it more. 0:56:22.920 --> 0:56:26.279 There definitely can be side effects, but I honestly just 0:56:26.360 --> 0:56:29.359 did not do a good job of looking into them 0:56:29.400 --> 0:56:32.600 as much. So I will get back to you on that. Okay. 0:56:33.840 --> 0:56:37.640 I'm not to have a question sort of like about lowering. 0:56:37.680 --> 0:56:41.880 So we've talked about lowering and the importance of having 0:56:42.120 --> 0:56:44.880 lower levels, but there is such a thing as too low. 0:56:45.160 --> 0:56:47.000 What are consequences of that? 0:56:47.200 --> 0:56:51.160 That's a great question. I don't have a number for you, Okay. 0:56:51.800 --> 0:56:57.080 What the data shows is that the higher your individual 0:56:57.239 --> 0:57:02.239 risk of cardiovascular disease, right, Because cardiovascular disease is not 0:57:02.520 --> 0:57:03.600 only cholesterol. 0:57:03.680 --> 0:57:05.640 No, no, no, I hope that I. 0:57:05.360 --> 0:57:07.680 Have made that clear. It is not by any means 0:57:07.680 --> 0:57:11.000 only cholesterol, but lower in cholesterol is one of the 0:57:11.040 --> 0:57:13.880 big ways that we have to reduce the chances that 0:57:13.920 --> 0:57:16.880 you're going to develop or have really bad outcomes like 0:57:16.880 --> 0:57:19.960 a heart attack or a stroke or death from cardiovascular disease. 0:57:21.000 --> 0:57:24.720 And so what we know is that the higher your 0:57:24.760 --> 0:57:27.200 individual risk based on all of your other risk factors, 0:57:27.240 --> 0:57:29.320 age whether or not you smoke, how much alcohol you drink, 0:57:29.360 --> 0:57:31.760 your BMI, your blood pressure, whether you're on a blood 0:57:31.760 --> 0:57:35.440 pressure medicine, your kidney function, based on all of those things, 0:57:35.840 --> 0:57:39.520 the higher your risk, the lower we need to push 0:57:39.560 --> 0:57:43.680 your cholesterol to really lower your risk of bad outcomes. 0:57:44.760 --> 0:57:47.520 So people who are very high risk, in the newest guidelines, 0:57:47.880 --> 0:57:50.160 people who are very high risk, the recommendation is to 0:57:50.200 --> 0:57:54.120 reduce their LDL to less than fifty five. And that's 0:57:54.320 --> 0:57:57.320 very low, and we haven't seen any bad outcomes from that, 0:57:57.480 --> 0:57:59.960 meaning we haven't found a number that is too low 0:58:00.880 --> 0:58:04.080 for those people who are very high risk, okay, but 0:58:04.240 --> 0:58:07.760 for other people, we haven't necessarily shown that there is 0:58:07.920 --> 0:58:11.960 a benefit to pushing them that low. And so for 0:58:12.040 --> 0:58:14.360 most other people, the recommendation is going to be either 0:58:14.720 --> 0:58:17.880 less than seventy or less than one hundred, depending again 0:58:17.960 --> 0:58:21.480 on what your risk is of cardiovascular disease development. 0:58:21.880 --> 0:58:26.120 Huh, yeah, So prolonged use of statins are like long 0:58:26.160 --> 0:58:27.160 time use of statins. 0:58:27.160 --> 0:58:30.240 Basically, if your blood cholesterol. 0:58:29.720 --> 0:58:31.000 Is high enough that you need to be on a 0:58:31.040 --> 0:58:33.000 statin or you are prescribed as statin. 0:58:33.280 --> 0:58:35.960 Or another lipid lowering medicine or something like that, you 0:58:36.040 --> 0:58:39.439 are on that regimen for the rest of your life. 0:58:40.000 --> 0:58:45.520 Often yeah, often, yeah, that because again that's the data 0:58:45.520 --> 0:58:47.920 that we have, right right, And we'll talk in a 0:58:47.960 --> 0:58:52.960 second about how much atherosclerosis is. It is a disease 0:58:53.000 --> 0:58:57.800 of long term right, Yeah, it's not a short term. 0:58:57.840 --> 0:58:59.760 It's not the rabbits that just get it in a 0:58:59.800 --> 0:59:03.320 week or two. It is a long term disease kind 0:59:03.320 --> 0:59:05.560 of thing, and so that is why it requires long 0:59:05.640 --> 0:59:06.320 term management. 0:59:06.560 --> 0:59:10.600 Plaques weren't built in a just like rome wasn't built 0:59:10.640 --> 0:59:11.400 in a thing exactly. 0:59:11.480 --> 0:59:13.760 Whatever, Yeah, isn't it a day? 0:59:14.880 --> 0:59:17.840 Probably I'm terrible with like saying so I thought I 0:59:17.880 --> 0:59:18.919 cannot remember them. 0:59:19.120 --> 0:59:20.840 I mix my metaphors constantly. 0:59:21.120 --> 0:59:26.200 I love it. I want to just briefly like, shout 0:59:26.240 --> 0:59:30.479 out is not the right word upon rage about rage 0:59:30.640 --> 0:59:33.240 or how sure because there is a lot out there 0:59:33.320 --> 0:59:37.040 right now on like, oh, alternative types of medicines to 0:59:37.520 --> 0:59:42.240 lower cholesterol. And I'm not talking about lifestyle interventions like 0:59:42.320 --> 0:59:44.560 diet and exercise changes. We already talked about those. They 0:59:44.560 --> 0:59:48.160 have decent evidence they're an important part of this. But 0:59:48.480 --> 0:59:51.480 one of the things that some people use or claim 0:59:51.720 --> 0:59:55.880 to have a benefit in lowering cholesterol are phytosols, right. 0:59:55.960 --> 0:59:59.919 Those are plant based cholesterols, and it is possible, based 0:59:59.920 --> 1:00:04.560 on on some like observational data, that consuming high levels 1:00:04.600 --> 1:00:08.760 of these plant based cholesterols or plant based sterols might 1:00:08.960 --> 1:00:12.280 decrease LDL cholesterol, especially when you look at people on 1:00:12.320 --> 1:00:15.800 like vegan diets who have quite a lot of phytosterol 1:00:15.800 --> 1:00:20.600 consumption or who are taking other additives of phytosterols. But 1:00:21.240 --> 1:00:25.160 we have no randomized control trial data on these, and 1:00:25.320 --> 1:00:28.040 the data that do exist, what's really interesting is that 1:00:28.200 --> 1:00:31.920 they seem to be most effective when they're consumed with meals, 1:00:32.080 --> 1:00:35.400 meaning when you're getting it from foods rather than just 1:00:35.720 --> 1:00:40.360 a supplement or an addition. And of course, as we 1:00:40.400 --> 1:00:42.520 talk about so often on this podcast, Aaron, there are 1:00:42.560 --> 1:00:47.720 no regulations on supplements, whether we're talking about phytosterols or 1:00:48.360 --> 1:00:53.080 other nutraceuticals. And one of the big ones out there 1:00:53.280 --> 1:00:56.439 for cholesterol is red yea's rice. You mentioned it erin. 1:00:58.000 --> 1:01:04.040 The mechanism of the compound produced by this yeast that's 1:01:04.080 --> 1:01:09.560 grown on rice is that it blocks hmg CoA reductastes. 1:01:09.800 --> 1:01:11.640 It's a statin. It's a statin. 1:01:11.840 --> 1:01:14.560 But okay, because it's coming from a plan, it's extracted 1:01:14.560 --> 1:01:17.480 from a plant. Plants produce different levels of these things, 1:01:17.520 --> 1:01:20.000 and so you have no idea how much you're getting, 1:01:20.360 --> 1:01:22.880 and so it can be dangerous. You could be on 1:01:23.440 --> 1:01:28.240 very low dose, non existent dose versus high intensity or whatever. 1:01:28.520 --> 1:01:31.000 And most brands in studies that have looked at this 1:01:31.160 --> 1:01:36.840 have no detectable levels of that actual compound. Right, There's 1:01:36.880 --> 1:01:40.959 no regulation on the composition of those particular supplements. There's 1:01:41.000 --> 1:01:43.760 no regulation on how much of that compound, like you said, 1:01:43.800 --> 1:01:45.960 the yeast is actually going to produce when it's fermented. 1:01:46.000 --> 1:01:49.000 So there's batch to batch variation, there's brand to brand variation, 1:01:49.160 --> 1:01:51.920 and at the end of the day, it's an unregulated statin. 1:01:52.840 --> 1:01:54.000 It's unregulated. 1:01:55.000 --> 1:01:58.280 Yeah, And I don't want to make that sound like, oh, well, 1:01:58.280 --> 1:02:03.560 pharmaceutical companies are just the best thing ever, Right, they're not. 1:02:03.880 --> 1:02:06.080 And it's also not the case that our guidelines might 1:02:06.120 --> 1:02:09.520 not be subject to some degree of bias because, like 1:02:09.560 --> 1:02:13.680 you mentioned, of the conflicts of interests that exist within 1:02:14.080 --> 1:02:18.560 cardiology and within like I mean, all fields of medicine. Realistically, 1:02:19.400 --> 1:02:22.040 a good number of the authors and the people who 1:02:22.040 --> 1:02:24.520 were involved in the peer review process for the newest 1:02:24.640 --> 1:02:28.360 DISSIPIDYMA guidelines in the US have financial conflicts of interest 1:02:28.680 --> 1:02:31.360 not just with pharmaceutical companies, but with imaging companies, with 1:02:31.400 --> 1:02:34.920 genetic testing companies. And that doesn't mean that all of 1:02:34.960 --> 1:02:37.800 our data that we have that is so strong isn't 1:02:38.000 --> 1:02:41.960 real or isn't strong, but it just muddies these waters 1:02:42.000 --> 1:02:45.520 even more and it creates this gap where people can 1:02:45.520 --> 1:02:50.960 really exploit that uncertainty totally. And it's really really a 1:02:50.960 --> 1:02:56.280 bummer because atherosclerotic heart disease, including heart attack and stroke, 1:02:56.480 --> 1:03:02.439 kills an estimated nineteen million people worldwide every year. As 1:03:02.480 --> 1:03:05.960 of the twenty twenty three Global Burden of Diseases study. Wow, Yeah, 1:03:06.200 --> 1:03:10.880 an estimated six hundred million people are living with cardiovascular 1:03:10.880 --> 1:03:17.080 disease right now every across the globe. Cardiovascular disease is 1:03:17.160 --> 1:03:20.920 the leading cause of disability just in life years. In 1:03:20.960 --> 1:03:24.840 some countries it is a third to forty to forty 1:03:24.920 --> 1:03:29.680 five percent of all deaths, and of course, especially in 1:03:29.720 --> 1:03:32.840 this country, the estimated costs to healthcare are in the 1:03:33.000 --> 1:03:38.960 hundreds of billions of dollars and an estimated eighty percent 1:03:39.160 --> 1:03:44.640 of this disease is due to modifiable risk factors and cholesterol. 1:03:44.720 --> 1:03:50.000 This relationship between LDL cholesterol and cardiovascular disease is so 1:03:50.360 --> 1:03:54.520 incredibly clear, and it is something that we really have 1:03:54.600 --> 1:04:01.680 the potential to treat right. So it's uh, it's such 1:04:01.720 --> 1:04:05.520 a huge bummer that there are so many people who 1:04:05.560 --> 1:04:09.920 do not have access to this right. And it's not 1:04:10.400 --> 1:04:14.240 just older adults. I think that we think of cardiovascular 1:04:14.280 --> 1:04:18.200 disease as something that only happens to older people. But 1:04:18.680 --> 1:04:21.680 the more that we look at and study the like 1:04:22.520 --> 1:04:27.440 pathogenesis of cardiovascular disease, the more we understand that especially 1:04:27.960 --> 1:04:32.520 cholesterol is a long term exposure that increases your risk. 1:04:33.480 --> 1:04:37.440 So having exposure to higher levels greater than one hundred 1:04:37.760 --> 1:04:41.520 of LDL cholesterol, especially greater than one sixty younger in 1:04:41.600 --> 1:04:46.200 life and for longer periods, increases your risk more than 1:04:46.200 --> 1:04:48.840 if it just goes up over time. If that makes sense, Yes, 1:04:48.880 --> 1:04:51.920 it does make sense. And it's estimated that twelve to 1:04:51.960 --> 1:04:55.480 thirteen percent of young adults have dyslipidemia in this country. 1:04:55.840 --> 1:04:56.120 Wow. 1:04:56.120 --> 1:05:00.160 So that's not a small number, right. It's estimated that 1:05:00.280 --> 1:05:03.520 in the US, if everyone, based on guidelines, who was 1:05:03.560 --> 1:05:07.080 recommended to be on medicine to lower their cholesterol was 1:05:07.160 --> 1:05:10.760 actually on a medicine for this, like a statin, we 1:05:10.840 --> 1:05:16.160 could prevent one million cardiovascular disease events like heart attack, stroke, 1:05:16.200 --> 1:05:20.520 and death in ten years. A million. Whoa Okay, And 1:05:21.720 --> 1:05:24.400 that's just in the US, where we have much better access. 1:05:24.440 --> 1:05:26.959 In low and middle income countries, it's estimated that only 1:05:27.000 --> 1:05:30.560 one in ten people who would be recommended to be 1:05:30.680 --> 1:05:33.120 on some kind of medicine to lower their cholesterol or 1:05:33.160 --> 1:05:37.080 actually on a medicine because they don't have access. Right. 1:05:38.200 --> 1:05:38.960 So that's a lot. 1:05:39.760 --> 1:05:41.360 It's a lot, Eric, It's a. 1:05:41.320 --> 1:05:45.640 Lot, but there is. I just think it's one of 1:05:45.680 --> 1:05:52.480 those situations where medicine has come so far, right, and 1:05:52.560 --> 1:05:57.480 the data that we have is so strong, but it's 1:05:57.520 --> 1:06:00.959 also not all just one thing, and I think that 1:06:00.960 --> 1:06:04.439 that is where some of the kind of confusion and 1:06:05.800 --> 1:06:09.000 uncertainty and doubt can come from. Right, Because we look 1:06:09.040 --> 1:06:12.520 at cardiovascular disease events over time, they're still going up, right, 1:06:12.800 --> 1:06:15.560 But we have these great medicines, but they're still going up. 1:06:16.640 --> 1:06:18.600 And that's because it is so many other things that 1:06:18.640 --> 1:06:20.440 play into it. So this was not an episode just 1:06:20.520 --> 1:06:25.760 only about cardiovascular disease, but cholesterol overall. And that is 1:06:25.800 --> 1:06:26.840 what I have to say Erin. 1:06:28.320 --> 1:06:32.480 It is really complicated and it's so recent, and I 1:06:32.520 --> 1:06:35.960 think that's what contributes a lot to this. And it 1:06:36.000 --> 1:06:38.640 does go to show that you can have the data, 1:06:38.800 --> 1:06:42.800 you can have the treatments, you can have the like 1:06:42.840 --> 1:06:47.480 all of these different facets of in support of this, 1:06:48.160 --> 1:06:51.600 and that's not enough. And so figuring out that gap 1:06:51.760 --> 1:06:54.360 what will make what will be enough? How do we 1:06:55.120 --> 1:06:57.400 actually either get the treatment to people who need it, 1:06:57.640 --> 1:07:00.160 how do we actually develop better treatments. 1:07:00.160 --> 1:07:00.960 Whatever it is? 1:07:01.320 --> 1:07:01.600 Right? 1:07:01.680 --> 1:07:05.000 How do we address those gaps where we're clearly failing. 1:07:05.360 --> 1:07:08.720 Yeah, yeah, it's a great Questionnaaring. 1:07:08.320 --> 1:07:09.600 Hopefully someone figures it out. 1:07:10.040 --> 1:07:14.040 Yeah. Do you want to read so many papers about 1:07:14.320 --> 1:07:17.520 how we got all of this information? We can tell you. 1:07:17.760 --> 1:07:18.440 We can tell you. 1:07:19.160 --> 1:07:22.360 I also want to shout out real quick too, that 1:07:22.800 --> 1:07:27.200 they're speaking like on the subject of misinformation and social media, 1:07:27.360 --> 1:07:32.280 wellness influencers, health influencers, stuff like that. There is Next 1:07:32.320 --> 1:07:36.560 week's book Club episode is an interview with Deborah Cohen. 1:07:37.040 --> 1:07:40.360 It's a book called Bad Influence, and it's really a 1:07:40.360 --> 1:07:41.480 fascinating conversation. 1:07:41.680 --> 1:07:42.800 Definitely tune in. 1:07:42.880 --> 1:07:45.240 There's a whole we have a little bit about Statin's 1:07:45.240 --> 1:07:48.840 in there, so check it out. Yeah, but papers for 1:07:48.920 --> 1:07:52.160 this episode, Okay, I have a bunch more again. I'll 1:07:52.160 --> 1:07:54.880 shout out again that Steinberg series from two thousand and 1:07:54.920 --> 1:07:59.120 four in Interpretive History of the cholesterol controversy, then by 1:07:59.360 --> 1:08:03.880 jew at All from twenty eighteen patient beliefs and attitudes 1:08:03.920 --> 1:08:07.360 just taking statins, and then by Endo a gift from 1:08:07.440 --> 1:08:09.800 nature the birth statins. So that's the person who. 1:08:09.880 --> 1:08:12.320 Oh I love it. Let me tell you where you 1:08:12.360 --> 1:08:15.240 can learn more. I really liked a paper by Silverman 1:08:15.360 --> 1:08:20.560 at All from JAMA twenty sixteen that was the association 1:08:20.640 --> 1:08:24.320 between lowering LDLC which is LDL cholesterol and cardiovascular risk 1:08:24.439 --> 1:08:27.960 reduction among different therapeutic interventions, A systematic review and men analysis. 1:08:28.000 --> 1:08:30.439 That's the one that has really great graphs, honestly on 1:08:30.600 --> 1:08:34.320 like with therabars and the risk reduction. Loved it. I 1:08:34.360 --> 1:08:36.920 have links to the newest guidelines as well too. The 1:08:36.960 --> 1:08:40.880 study looking at the overall risk of cardiovascular disease and 1:08:40.920 --> 1:08:44.800 heart attack was from the Journal of American College of 1:08:44.840 --> 1:08:47.040 Cardiology from twenty twenty three, and that was one of 1:08:47.080 --> 1:08:50.040 the global Burden of Disease studies, so we have that one. 1:08:50.400 --> 1:08:53.200 There's also that twenty twenty two paper by wreath at 1:08:53.240 --> 1:08:55.439 All in the Lancet that was the effect of Statin 1:08:55.479 --> 1:08:58.719 therapy on muscle symptoms and individual participant data meta analysis 1:08:58.760 --> 1:09:02.400 of large scale, randomized double blind trials. But honestly, there's 1:09:02.439 --> 1:09:06.320 so much more there, Aaron, so you everyone can check 1:09:06.360 --> 1:09:08.400 it out on our website this pocastikadi dot com under 1:09:08.479 --> 1:09:09.240 the episode stap. 1:09:10.000 --> 1:09:12.559 Thank you to Bloodmobile for providing the music for this 1:09:12.640 --> 1:09:14.360 episode into all of our episodes. 1:09:14.880 --> 1:09:18.360 Thank you to Leanna and Tom and Mark and Jessica 1:09:18.439 --> 1:09:20.880 and everyone at exactly Right for everything that you do 1:09:20.920 --> 1:09:22.200 to make this podcast possible. 1:09:22.320 --> 1:09:27.960 Thank you, thank you, and thank you to you listeners, subscribers, watchers, 1:09:28.000 --> 1:09:32.040 et cetera. We appreciate you engaging with this podcast so much. 1:09:32.080 --> 1:09:33.720 I know it sounds so clinical when I say that, 1:09:33.760 --> 1:09:37.240 but what I mean is, like anyone who like follows 1:09:37.280 --> 1:09:39.480 us on social media, yeah, whatever. 1:09:39.400 --> 1:09:41.479 Anyway it is, it truly means everything. 1:09:41.840 --> 1:09:45.000 Thank you, thank you, and thank you as always to 1:09:45.080 --> 1:09:47.120 our patrons for your support over on Patreon. 1:09:47.439 --> 1:09:48.760 It means like it. 1:09:49.520 --> 1:09:52.240 I can't believe that you're supporting us there. Thank you. Yeah, 1:09:52.280 --> 1:09:53.160 it really means a lot. 1:09:53.720 --> 1:09:56.160 Until next time, wash your hands. 1:09:55.920 --> 1:09:56.919 You feel the animals. 1:10:01.600 --> 1:10:17.200 Oh Buba buba bumbo ombu