**EP269: Talking Brain Natriuretic Peptides & LDL, HDL, and VLDL Cholesterol** **Dr. Auric Bishop:** Welcome, my name is Dr. Auric Bishop. I'm a cardiologist, an author, and a keynote speaker. I'm the CEO of the Healthy Heart Network. I'm all about trying to help people live as well as possible for as long as possible. Heart disease is huge in Australia. Every 20 minutes, someone suffers a heart attack. Most of these could probably have been avoided if only we knew what to do. This podcast is all about helping you understand blood pressure, weight, and cholesterol for better health. If you enjoy this podcast, I would be honored for a five-star review. You can share it with your family and friends. It may well save someone you love. **Dr. Eric Bishop:** Hi, my name is Dr. Eric Bishop, and today I'd like to talk about the brain natriuretic peptide system, also referred to as the natriuretic peptide system. Well, what is it all about? Well, it turns out that when the heart is under strain, it releases its own chemical messengers, and those chemical messengers are called peptides. These peptides literally have a role to reduce the strain on the heart. The very things that they do will offload the heart and improve its function. Brain natriuretic peptide, as you can probably guess, leads to naturesis, and naturesis is really the same as diuresis. So these peptides will lead to fluid loss through the kidneys—naturesis. They'll drive the blood pressure down a bit, thereby reducing the work that the heart has to do. They actually dampen down sympathetic tone. Think how valuable that would be for a heart that is under load or under strain. They turn down aldosterone production. And aldosterone, as you would be aware, leads to sodium retention. Sodium retention leads to fluid retention, which leads to raised blood pressures and more strain on the heart. So it reduces aldosterone. You can see how these natriuretic peptides facilitate reducing stress on the heart. They've also been shown to reduce inflammation, so they can reduce scarring in the heart and, importantly, can even have a positive effect on remodeling of the heart if it's been damaged and then recovers. So where do we use these natriuretic peptides? Well, we certainly use them in the acute setting in accident and emergency departments when there's a question as to what might be causing the symptoms for an individual who's presented with shortness of breath. We're asking the question, could this be related primarily to the lungs or primarily to the heart? Testing the brain natriuretic peptide levels gives us a lot of clarity in that space. If those brain natriuretic peptide levels are very high, then this person has problems with their heart. If the levels are low, then this person has problems with their lungs. So it's extremely useful in that situation. In fact, there is a Medicare rebate to allow access to that testing in the acute setting in a hospital setting. Unfortunately, in the community, there isn't the opportunity to access a rebate for that testing. So if you thought for clinical purposes it was a valuable test for your patient to clarify whether shortness of breath was lung or heart-related, that patient would have to cover that cost out of pocket. Brain natriuretic peptide is also used in specific circumstances to track cardiac failure, and some clinics will do that with some regularity to demonstrate that the high levels at the time of presentation have been brought under control and have then remained stable with the therapeutic interventions put in place. In my own practice, one of the situations that I use brain natriuretic peptide measurements is in patients with significant valvular abnormality who are not yet ready to go to surgery. So think about someone who has severe aortic stenosis, but not critical, who is essentially asymptomatic. As I follow these people on a yearly basis with ultrasound, I tend to combine that with the brain natriuretic peptide measurement. That gives me two points of reference. If the ultrasound looks worse and the brain natriuretic peptide measurement has worsened, then we're pretty sure things have changed. If the echocardiogram looks better, but the brain natriuretic peptide looks worse, it may be an error in the measurement of the echocardiogram. If the echo looks fine and the brain natriuretic peptide looks stable, then we can be fairly sure things have remained stable for that patient, assuming that their clinical status has also remained stable. Well, one of the important things about the brain natriuretic peptide system, or the natriuretic peptide system, is that it is broken down in the body by the neprilysin system. You don't necessarily need to remember that, but the neprilysin system is the enzyme system that breaks these factors down. Well, that is important in the current management of cardiac failure because we have an agent that blocks neprilysin. It's an inhibitor of neprilysin, and the consequence of that is that the body's level of natriuretic peptides is elevated as a consequence. As we've just talked about, these natriuretic peptides are beneficial for naturesis, lowering blood pressure, reducing sympathetic nervous system activity, decreasing aldosterone production, remodeling, and reducing inflammation. So having these peptides at higher levels and not being broken down can be extremely valuable. The agent we use for that is Secubitrol, and we see it in a preparation called Entresto. This is a very important pillar of the management of cardiac failure, and you will see it used regularly in situations where people have diminished left ventricular function. Its role is raising those good natriuretic peptide tonics for the heart. You've probably guessed, if you think it through, but if you use a neprilysin inhibitor, then your brain natriuretic peptide, of course, by default will go up because you're reducing its breakdown. You can get around that, and if you use NT Pro BMP, which is a precursor, then this is not impacted by the neprilysin system and gives a clearer, less distorted indication of where the natriuretic peptide system is sitting in an individual who's been put on a neprilysin inhibitor. Anyway, there's a spiel on the brain natriuretic peptide system, which really offsets and protects the heart. I hope that's made a bit of sense to you. Today, I'd like to talk about something that comes up with some regularity, and that's people asking questions about what is LDL, what is VLDL, and what is HDL? Well, it's important to understand that these are lipoprotein particles, and if you like, they are the carriers of cholesterol and fats around the body. These are made up of a phospholipid bilayer, and they come with different densities. So that bilayer, if you like, is like a stretchy bag that wraps around the contents, which could include triglycerides and cholesterol esters. As the cholesterol esters are given up and the triglycerides are given up, the sack around shrinks down, and the density increases. As you put more and more particles into the vehicle, it swells and gets larger. I often speak with people about these lipoprotein particles and describe them a little bit like motor vehicles. They have different densities and carry different amounts of particles. So a very low-density lipoprotein is a large particle. Think of a bus with scattered cholesterol and triglyceride passengers in there. As that bus drives along and starts to give up some of its particles, it gets smaller—magically. It gets smaller to, if you like, a minibus or a large family vehicle carrying a large family sedan. Now it's still carrying cholesterol and triglyceride particles, but it's become denser. It's now a low-density lipoprotein. Now imagine that it offloads even more passengers, and now it's down to maybe a mini minor. This is now a mini minor with some cholesterol and triglyceride passengers in it. This is now a high-density particle. Interestingly, this high-density particle can now pick up cholesterol from the periphery and bring it back to the liver. So the less dense, larger particles tend to offload their cholesterol load, their passengers, if you like, and the more dense particles will pick up and reverse transport cholesterol back to the central depot, which in our bodies is the liver. So when we think about the significance of these, all of our research around plaque in the arteries and coronary artery disease has really focused on the low-density lipoprotein as the main particle contributory to plaque formation. We know that getting that LDL cholesterol down one millimole per liter for someone at high risk offers that individual a 20% relative risk reduction. So it's pretty important we continue to monitor lipid panels, particularly in our patients who have had some sort of coronary event. We ask not just for total cholesterol and triglycerides because that doesn't give us the full picture. We need to ask for a full lipid panel. So LDL is really tied in with plaque and coronary artery health. We really want to drive that down in individuals who've had an event, ideally to less than 1.8 millimoles per liter if we possibly can. HDL is the reverse transport particle that I touched on. Now, this is really complicated. Measuring it is sort of interesting, but the reality is there are about 200 different variances of HDL, and some work very well, some don't. We don't know within an individual on the very simple blood tests that we do whether we've got a very active HDL or not. So in terms of HDL, I tend to look at it not in absolute terms but in terms of triglyceride levels because as we see triglycerides increase, we often see HDL go down, and that is a message that we've got a hyperinsulinemic state. VLDL, we don't necessarily measure that particle directly, but we do measure triglycerides, and VLDL is elevated when we see raised triglyceride levels. The main drivers for that would be insulin resistance, alcohol, and obesity. Really, that raised triglyceride level with the reduced HDL is a flag for metabolic syndrome, generally associated with central adiposity and features of inflammation, even high blood pressure and raised sugar levels. So that's LDL—think about plaque. HDL—think about its levels and whether it goes down as the triglycerides go up. And VLDL, which is really the main carrier of triglycerides around the body, we see it particularly high after meals. That's where we tend to do fasting bloods to get a better feel for triglycerides when we're measuring that. In my own practice, I take the opportunity to do fasting bloods. I know there's a lot of conversation in the media and in journals about whether we need fasting bloods for lipid management. My own practice, though, is that I prefer to take a fasting blood, and I will do a lipid profile. Make sure you ask for that. I’ll do simultaneous blood sugar levels, glucose, and I’ll do simultaneous fasting insulin. That fasting glucose and insulin can be put into an equation called a HOMA equation—H-O-M-A. Look it up if you're interested: Homeostatic Metabolic Assessment. I can't remember the exact figures, but basically, you can put those figures into a very simple calculation to offer at least a feel for potential insulin resistance. So I think checking the lipid profile simultaneously with looking for insulin resistance is a really important way to cover a more holistic approach to risk management. Well, I hope you've enjoyed this short spiel on LDL, HDL, and VLDL. If you have any queries or questions, of course, please feel free to be in touch. For now, I'm going to wish you the very best. Take care and bye for now. Join the Healthy Heart Network and become part of our growing community. Do you want to know more about your heart health and your risk of heart attack? For $5, get lifetime access valued at over $55. The Healthy Heart Network has been designed to support and help you understand your risk of heart attack, your risk level where you are right now, and the positive steps you can take to reduce that risk. 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