Hi, my name is Dr. Oreck Bishop and welcome to my podcast and videocast station. As always, I'm super grateful that you've taken a moment to tune in and I really do appreciate that these days we have very little time. So if you're taking your valuable time to listen to this, I don't take it for granted. Thanks very much. Look, today I'd like to talk about some of the conditions and some of the drugs that are associated with raised cholesterol levels. And this is a really interesting space because, of course, we know about cholesterol levels being elevated. We know they run in families. We know it can be genetic. monogenic and polygenic. And most of us have, with raised cholesterol, have polygenic elevated cholesterol. Well, that's when you get a little bit from both sides, a little bit of inheritance from both sides and your cholesterol levels are up. Well, of course, there's the monogenic form of increased cholesterol called familial hypercholesterolemia. where you really receive a significant defect of one of your receptor genes from one of your parents. And that leads to very high levels of LDL particles and therefore LDL receptors. in the bloodstream now i'm not going to talk about that particular condition today i'm going to talk about all the other conditions because there's plenty of them so if your cholesterol is elevated it's pretty important that your doctor who's thinking about managing that cholesterol thinks about some of the other things that could be driving it so i'm going to talk about the conditions the medical conditions that can be associated with that. I'm also going to talk about some of the drugs that are going to be associated with that. And there's a little piece on coffee right at the end. So if you're a bit like me and enjoy your cup of coffee first thing in the morning, stay tuned right to the end because there's a little piece about that as well. Well, when we think about the sort of conditions that can lead to raise cholesterol in an individual, The very first one that we often think about and test for is hypothyroidism. This hypothyroidism seems to have an impact on the LDL receptor. So we talk about this particle or ApoB protein particle that carries cholesterol around. Hypothyroidism reduces the effectiveness of that protein. And as that protein becomes less effective, that receptor becomes less effective. It's less able to pull LDL cholesterol into the liver. Consequences, more in the bloodstream, elevated LDL and LDL-C levels. So hypothyroidism, pretty easy to check for. We check thyroid stimulating hormone. It's a simple blood test. And certainly if someone's had problems with their thyroid in the past, really important to check it. Well, diabetes, we know diabetes is a big player for cholesterol levels and it tends to be associated with raised triglycerides, lower high-density lipoprotein or lower so-called good cholesterol, and also tends to be associated with the smaller, denser type of LDL particles. So we see a change in the lipid profile with diabetes. Chronic kidney disease is the next one that we really have to be aware of. We know that kidney disease is closely linked with cardiovascular disease. And in the particular situation where someone with kidney disease has what's called nephrotic syndrome, and if you don't know what that means, nephrotic syndrome simply means that these individuals are losing lots and lots of protein out through their kidneys. The upshot of that is significant elevation of cholesterol particles in the bloodstream. It turns out that as the kidney loses these proteins out through the urine, the liver sort of responds by producing more and more proteins to try and keep up. While some of the proteins it produces are the proteins that carry cholesterol around. And so nephrotic syndrome can lead to very high cholesterol levels. Remember, this is a big issue because chronic kidney disease with all its associated metabolic issues is a significant driver for risk of heart attack. Well, we've talked about a couple of systems going wrong that can impact cholesterol. Well, the other one is liver disease itself. So as we see people with fatty liver, there's a metabolic or cardiometabolic access, if you like, where there's derangement of how things start to work. Fatty liver disease. Well, we call it non-alcoholic fatty liver disease. It's now changed its name to metabolic associated fatty liver disease. This condition will see triglycerides creep up, LDL creep up at the same time. All this contributes to the cardiovascular risk for these individuals. Almost paradoxically, in the end stages, as synthesis and function of the liver drops off towards cirrhosis, the cholesterol levels come back down. But this is really a very late stage and in no way a good sign for the individual. As you might imagine, there are other hormonal things that can drive cholesterol up. And one of them is when there's... elevated cortisol levels all the time from a condition where the glands are producing excess cortisol we know we all know cortisol is the stress hormone and it gets us a bit um well as we get fired up our cortisol levels increase well those cortisol levels will act a lot like steroids or prednisolone and they tend to raise triglycerides and raise ldl particle numbers and We call that raised cortisol level Cushing's syndrome. Cushing's syndrome, because he was the person who first described it. And these people, because of that long-term exposure to steroids, have characteristic features. They lose some muscle mass. They become centrally obese, central adiposity, like an apple, if you like. They often can have a hunch on their back. have increased facial hair as well. So they, with all that, tend toward diabetes, but they also throw their lipid profile out. Menopause, the decline in estrogen also plays into increases in LDL cholesterol and HDL cholesterol seems to drop away. So as menopause affects women, During that transition of life, those ladies will often see their cholesterol levels alter in proportion to that. So keep an eye out for all those medical conditions. We mentioned familial hypercholesterolemia. That's another story, but hypothyroidism, diabetes, kidney disease, liver disease, Cushing syndrome, and menopause. Well, when we think about... things that can impact cholesterol. The other thing that we really need to think about is what drugs could have a role. Well, I've just spoken about Cushing's syndrome and increased cortisone or pregnisolone type drugs in the bloodstream. Well, of course, if we think about the medications that can impact cholesterol and blood lipid profiles, well, steroids are pretty well right at the top. These fellows are really good to use for the short term if you really, really need them, really good to avoid for the long term. They significantly elevate LDL cholesterol, significantly elevate triglycerides and will drive people to obesity, diabetes, osteoporosis, you name it, steroids. If you can avoid them, try and avoid them. So they're number one on the hit list. Proteases. Now, you may not know what proteases are, but they're the group of drugs commonly used for treating HIV infection. So these individuals will be on long-term HIV therapy. And with these protease inhibitors having an impact directly on LDL cholesterols and triglycerides, it means these people will be carrying greater... exposure to these sort of lipid panels, these sort of lipid profiles, together with having an inflammatory condition underpinning it. These people run an increased risk of cardiovascular disease. Some of the antipsychotic drugs can also impact and increase cholesterol and triglyceride levels. This is really important because we know mental health. And when we talk about antipsychotics, these are the drugs used to treat schizophrenia and major depression. These conditions are really closely linked with increased risk of cardiovascular disease. So it's a concern that the very agents that are needed to help these people with these mental conditions can also drive up cardiovascular risk. Some of the beta blockers have had a role in altering blood lipid profiles, but the newer ones really don't seem to fall into that category. Thiazide diuretics. have a tiny effect and really not particularly significant. They could play into small changes in individuals where we're really trying to drive a target, but we also need to control blood pressure therapies. The oral contraceptive pill can also impact lipid profiles. So be aware of that. And this is important because women will be on this medication for an extended period of time. Well, there's one drug left that I'm pretty keen to talk about, and it's the one that most of us probably start the day with not thinking about our cholesterol levels at all, and that's coffee. And in coffee, there is a compound called cafestol. Now, cafestol is one of the organic molecules that's within coffee, but it gets filtered out. often depending on how that coffee is produced. So where the coffee and the beans are not particularly filtered in the process of making a cup of coffee like French press, espresso and Turkish coffee, then hephistole levels can be pretty high. It seems to interact with bile acid metabolism and it alters liver receptors that regulate cholesterol levels and increase. LDL cholesterol, five or six cups of cafestol rich coffee per day can increase cholesterol levels between five and 10%, which is a bit. It's nearly the same as doubling a statin dose in actual fact for the reverse effect. So if we double a statin dose, we can often get five to 10% better lowering of a cholesterol level. But if we skip our five to six unfiltered coffees a day, we can increase our aldeol cholesterol by about five to 10%. So keep that one in mind. If you are a big coffee drinker and your cholesterol is really a problem and you're looking for any small gains, maybe filter your coffee a little bit more. So drip filtered will work well. But thick Turkish coffee, French press and espresso. Probably going to have a fair bit of the old cafestol in there. So go easy, go careful. Well, I'm going to wrap it up there. I think that's about as much as I would like to share about LDL and lipid profiles and medical conditions and drugs. And, well. I hope you found that interesting. I think it's really fascinating to think of some of the things that can feed into those lipid panels that we are constantly looking for and checking. So for now, I'm going to leave it there. I do hope you found that interesting. Please don't stop enjoying your cup of coffee in the morning on my behalf. Till next time, I do hope you live as well as possible for as long as possible. Take care and bye for now.
