Transcription:
Statins as Treatments in Cardiovascular Disease

Alyne: Lowering your cholesterol to a safe level is essential to protecting your heart. Welcome to our Health Track podcast. I'm Alyne Ellis. I'm here today with Dr. Anthony Patrello, the Medical Director of the Cardiovascular Institute at Montefiore St. Luke's Cornwall. Thank you so much for joining me today.

Dr. Patrello: Thank you so much for having me.

Alyne: Let's start with what is cholesterol?

Dr. Patrello: Cholesterol is lipoproteins that are in the body that are made by the liver, also absorbed by the gut through the diet. The issue with cholesterol is that they can build up in the vascular system in the body. Pretty much any place where there are blood vessels, there could be buildup of cholesterol including in the neck and in the brain, which can lead to stroke; including in the heart, which can lead to heart attack; including in the kidney arteries; the arteries in the belly, can lead to mesenteric ischemia; and including the arteries in the legs, which can lead to peripheral arterial disease.

So lowering cholesterol and keeping it in check primarily through diet, but also occasionally through medication is an important way in preventing clinical events in the future.

Alyne: So there are two kinds of cholesterol, as I understand it, HDL and LDL. Can you tell us what those are and if they're good or bad for us?

Dr. Patrello: Sure. So the LDL is the major component of your bad cholesterol. And that's going to be the cholesterol that's "atherogenic," that's the cholesterol that's going to deposit in the lining of blood vessels. The HDL is a good cholesterol. It's thought that it may actually help clear some of the bad cholesterol out from the circulation. So there is some protective effect from HDL.

Alyne: So when we have a blood test to check these levels, what numbers should we hope to see on the results?

Dr. Patrello: That's a great question and it's a complicated question. There is actually no absolute number that's right for everybody. It truly is a tailored therapy per individual based on their risk factors. So for example, using two extremes at the end of the spectrum, somebody who is a younger person in their twenties with no risk factors, no family history of any heart issues, very healthy, active, I may be happy with an LDL cholesterol in the 130s.

On the other end of the spectrum, somebody who's in their 80s, who's had a couple of heart attacks, had a stroke, peripheral arterial disease, is a vasculopath, has had a number of cardiovascular events. That's somebody who we want their LDL cholesterol to be far lower, ideally less than 70, but there really is no bottom number. The lower the number in that case, the better.

And then there's all grades in between. So it really is really based on your risk. So how do we define that risk? One of the primary ways that we use to define the risk is using the ACC risk calculator. It's a calculator that is available. You can Google, it's available on the internet. And it's produced by the ACC and it will tell you what your 10-year risk of having a cardiovascular event is.

Over 7.5% is considered to be a higher risk. Between 5 and 7.5% is considered to be an intermediate risk. So somebody who we want to target for very low LDL cholesterol would be anybody who has that ten-year risk over 7.5%. If you are a diabetic, that automatically puts you into the higher risk category. And if you have an LDL cholesterol of over 190, that automatically puts you in the higher risk category as well. And obviously if you've ever had any clinical cardiovascular events or known history of coronary artery disease, that would put you in the higher risk category as well.

in terms of the HDL cholesterol, you'd like that to be over 40. We tried to mostly target that through lifestyle change, through dietary changes, mostly through regular exercise can really help boost your HDL cholesterol.

Alyne: Now, when we have those blood tests, the other things that come back are the measurements for triglycerides. And what are those?

Dr. Patrello: Triglycerides are another component of the cholesterol. That's very much diet-related. It's very much carbohydrate in particular related. So a high carb diet tends to increase your triglyceride levels. Very high triglyceride levels can often correspond if you also have a low HDL cholesterol with something called metabolic syndrome, which is on your way to becoming a diabetic. So that's a common pattern that we see in diabetics, because they have abnormal production of insulin and abnormal metabolism of carbohydrates and sugars in particular. So they tend to have higher triglyceride levels and lower HDL levels.

And it's something that also we try to mostly target that through diet. There are some medications that can help triglycerides. There've been studies most recently, looking at Vascepa trying to treat triglycerides. It's actually shown a benefit in patients who have a history of coronary disease with a high triglyceride level. So there are some medications that we can use for that as well.

Alyne: Now, some of these numbers can be affected by what your history is, in terms of your medical history related to your family and inheritance.

Dr. Patrello: Absolutely. So there is a condition called familial hypercholesterolemia, which is a genetic predisposition to having high cholesterol levels. And there's all sorts of hereditary cholesterol conditions. There's familial hypertriglyceridemia as well. And so there is some of it that is in your control, but there are certain patients that no matter how good their diet is and how much they're exercising, that they are just genetically predisposed to having very high LDL cholesterols.

Alyne: And one of the problems is that we don't have any symptoms when we are having this damage and buildup in our arteries.

Dr. Patrello: Yeah. That's exactly right. So early on in the process, there's really a lag of decades between the time that your cholesterol starts to become elevated 'til the time that it deposits enough that you're actually developing clinical symptoms from it. And that lag is literally decades long.

So in that vulnerable period, that early stage, you don't know that your cholesterol is high unless you get it checked. You're not having any symptoms so it's easy to be complacent about it, but that really is the moment where most of the interventions can be helpful.

Alyne: So when should you start to get your cholesterol level checked? At what age?

Dr. Patrello: Yeah, there's really no absolute cutoff for that. Certainly by age 40, you should have it checked if you have a family history, that's going to play a major role in that as well. If you had a family member who had a heart condition in their thirties, I would certainly recommend getting it checked earlier than obviously in your low thirties.

At least probably anybody who's going to see a primary physician over the age of 18 should probably at some point at least get it checked at least once to see what it is and then probably more regularly as you get older into your forties and the frequency would be really tailored to your risk factors and family history.

Alyne: And how often do you recommend that you have it checked once you start that process?

Dr. Patrello: It totally depends on what the risk profile is. If it's somebody where I'm following this and making adjustments to medicine, at least annually. If I've made an adjustment to medication, then I'll often check between six and twelve weeks after the adjustment the medication was made. But at the very least, annually just to peek in to see where we're heading with things.

Alyne: And let's talk about medication for a minute. When do you decide to put someone on? I guess obviously part of it is family history. But tell us a little bit about the medication, when you decide to use it and if it has any side effects,

Dr. Patrello: So the most important thing that we're looking for in a cholesterol profile is lowering the LDL cholesterol. Triglycerides are important as I mentioned. There is a study called REDUCE-IT that actually did show a reduction in vascular events with lowering triglyceride levels, but mostly we're targeting the LDL cholesterol, trying to keep that down and keep that in check.

So the decision to treat really is based on whether or not looking at primary prevention or secondary prevention. So primary prevention means that somebody hasn't yet had a clinical event and I want to prevent a clinical event from happening. Secondary prevention means that somebody has already had a clinical event and I want to prevent the next clinical event from happening. So obviously the secondary prevention group is going to be far stricter and more aggressive because they've already had their clinical event than the primary prevention group.

But even in the primary prevention group, there is a ton of data to suggest that lowering LDL cholesterol is beneficial. The data that is the most supportive of which medication to use to lower LDL cholesterol is with statins. There's a lot of medications that can lower their cholesterol, lower the LDL cholesterol, make the number look prettier on the lab sheet. But there's a difference between making the number look better and actually reducing clinical events. What we actually want to do is to reduce clinical events. And the most amount of data, by far the most robust amount of data is the use of statin medications.

And the statins are medications that inhibit an enzyme that causes creation of LDL in the liver and the statins prevent that from occurring. In primary prevention, there were several studies that showed even for patients who haven't had a clinical event, reduction in events. For pravastatin in the West of Scotland trial, for lovastatin in the AFCAPS/TexCAPS trial, for Crestor in the Jupiter and HOPE-3 trial, all showed reduction in major cardiovascular events for people who actually never had one before and statins were shown to reduce those events.

In fact, there have been meta-analyses that looked at over 300,000 patients, who have been tried on statins and they show a significant across-the-board reduction in major vascular events, whether that's cardiovascular death, acute coronary syndrome, which is like a heart attack, getting stents or even strokes. And then when you decide, there's a question on when do you decide to treat and how low should you go with the numbers.

When you decide to treat is really based on that risk profile that I mentioned, that 10-year risk profile. If you have a ten-year risk, ACC ten-year risk over 7.5%, you're probably going to opt to treating your LDL cholesterol at that point. If that risk is between 5 and 7.5%, so you're in the intermediate risk category, we often try to use some tiebreakers to try to figure out whether or not the patient needs to be treated, sort of risk modifiers.

So some risk modifiers can be biochemical, so things that we checked in the lab test such as lipoprotein analysis whether or not the particles are small and dense, which are more atherogenic or they're large and buoyant, which are less atherogenic or less likely to produce cholesterol. We look at CRP, which is a marker of inflammation. The earliest sign or the earliest events that happen in the cascade for cholesterol buildup in the arteries is an inflammatory process. So an elevated CRP can be indicative of somebody who's vulnerable. Another is Lp(a), which is a type of LDL particle which is particularly atherogenic. So sometimes we use those as tiebreakers.

Other times, we use something called a coronary calcium score, which is like basically a CATscan done without contrast to see if there's any early evidence of plaque buildup in the arteries, very early on. Way before you can detect anything on a stress test, a calcium score can be indicative of buildup. And then how low that you go, it depends on what those answers to those questions were and how bad the answers to those questions were, how bad your calcium score was and things of that nature.

If you're deciding to treat, generally you're striving for between a 30 and 50% lowering of LDL. So whatever your cholesterol was to start with, you like it to be 30 to 50% lower than what your starting was. And if you actually have known vascular disease and, through all this we found that you actually did have some coronary disease, your calcium score was high, you try to get that LDL down as low as you can get it, ideally below 70.

There's never been shown a floor. Every study that has ever been done has shown that the lower the number, the better without a floor. Even below 40 has been shown to have benefit even as you get below 40.

Alyne: Well, now when you take a statin, do you have any side effects from that?

Dr. Patrello: Yeah. That's a great question. So that is the biggest struggle or one of the biggest struggles I have in my practice is when we make a decision with a patient, which was a shared decision-making to go ahead and to start medication, patients are very concerned about the possible side effects that can occur from statins. They've either talked to people or read some things on the internet about having some intolerability to the statins.

The major adverse effects, which are listed for statins mostly would be myalgias or muscle aches. And that occurs in about 10% of people. It's usually mild. There is a clinical phenomenon called rhabdomyolysis, which is breakdown of muscle. That is a serious adverse effect. And I think that is what patients are mostly worried about having when they have their muscle aches. But it's important to recognize that actual clinical serious muscle breakdown, that rhabdomyolysis, actually occurs on the order of like one in a hundred thousand times or basically 0.0001% of the time. It is not common.

So most of the muscle aches are mild and they can be managed. Other issues to look for is elevation of liver enzymes, which can happen only in about 1% of people and we oftentimes peek in on liver enzymes periodically just to make sure that there's no elevation. So the big struggle that I have is that it almost seems like a self-fulfilling prophecy, is that patients are worried about having these muscle aches. And then invariably within a couple of weeks of taking the medicine, they're having the muscle aches. And the question is are they truly having the muscle aches or was this sort of a self-fulfilling prophecy because that's what they were expecting.

This past November at the American Heart Association, at the AHA Meeting, there was a late- breaking clinical trial that was presented there that really I think helped answer this question. And I thought it was a wonderfully designed very creative trial. It was called the SAMSON trial. And what the investigators did was that they took 60 patients and they gave each of the patients 12 bottles. And the patients were going to take each bottle once a month for 12 months, so 12 bottles for 12 months.

And in these bottles four contained atorvastatin at a dose of 20 milligrams, four bottles contained placebo or a sugar pill and four bottles were completely empty. And the patients were going to take these bottles completely randomly and they we're going to report on what their side effects were in a zero to a hundred scale. Zero meaning that they had no symptoms and a hundred being that they had the worst muscle aches that they've ever had.

And the patients didn't know what was in the bottle except when it was empty. But they didn't know whether it was the placebo or the atorvastatin when they were taking those bottles that had a tablet and they recorded this. And what it actually ended up showing was that the patients had the exact same type of symptoms whether or not they were taking the placebo pill as if they were taking the statin medication. The same. In fact, over about a third of the patients had such serious effects that they felt from taking the medication, they actually had to stop taking the medicine. But that occurred just as often when they were taking the sugar pill as it was when they were taking the statin medication

Alyne: That's interesting, our perception of what we think we're experiencing when in fact our mind is telling us something. Let me just ask you is there anything when you are taking this medication that you need to avoid? I've heard for example, and maybe this is just a rumor, that it's not safe to eat grapefruit when taking a statin.

Dr. Patrello: So the issue with grapefruit juice is mostly with a particular enzyme that is used to break down the statin medications. That's the CYP3A4 enzyme. And that is mostly for medications of lovastatin, simvastatin and atorvastatin because you can increase the levels of those medications in the body because of the inhibition of the breakdown from the grapefruit juice. But really that's for somebody who is drinking gallons and gallons of grapefruit juice.

Usually, if you're having less than eight ounces of grapefruit juice a day or a glass of grapefruit juice a day, that's going to be okay. If you really love it, should you drink a half a gallon of it if you're on lovastatin, simvastatin or atorvastatin? Maybe not. It may predispose to some more of these muscle ache effects. If that's a major issue, there are other statins out there such as Crestor or pravastatin that could be switched to if that's a major issue.

Alyne: Anything else you can't eat in gallons and gallons of materials?

Dr. Patrello: Well, I guess what I would say is that a lot of patients feel that, "Oh. Hey, since I'm taking a statin now, I don't have to watch my diet anymore and I can eat as much hamburger and red meat as I'd like." And I would argue that you're going to be able to out eat your medicine. So it's important that if we decide to treat you with medication, that you still do your part with lifestyle change as well and we're not just relying on the medication solely

Alyne: And that doesn't just include red meat, it also includes a butter I think and a few other items that are really on a no-no list.

Dr. Patrello: Sure. Yeah. Again basically, my approach for patients from a dietary standpoint, I try not to say that there is anything that is completely off limits. When you decide that you're going to pursue lifestyle change and dietary change, essentially this should be a lifelong change for the rest of your life. And I'm not sure anybody would be very happy if they really like steak to tell them that they can never have steak for the rest of their life. I mean this seems a little bit unreasonable where you can never have anything that has butter for the rest of their life.

So basically what you do is you try to pick the things that are important to you and include those in your diet. Eliminate the things that were really not important to you to begin with that are high in cholesterol and pick your spots and try to keep things in moderation.

In general, you want to keep more toward more of a Mediterranean-type diet So fruits, nuts, grains, vegetables, lean chicken, fish, olive oil-based products, things like that.

Alyne: Now, finally, once you've gotten your artery somewhat clogged here, is there any way to undo that damage?

Dr. Patrello: That's a good question. So if you already to start to develop blockage, although lifestyle is important, we're a little bit past the point of just sticking with lifestyle alone. At that point, data would strongly suggest that starting a cholesterol-lowering medication and in particular starting a statin medication.

And the goal of statins would be to lower the LDL cholesterol to prevent any further plaque progression. So if there's a 50% blockage, hopefully you're going to prevent that from becoming 60 and 70% down the road.

Could there be some plaque regression? Maybe a little bit. In studies that have looked at the carotid arteries, which are very easily imaged through ultrasound, there have been shown to be a little bit of plaque regression with the use of statins over time. It's not robust regression, so you're not going to go from a 50% blockage to a 10% blockage, but you can get some plaque regression.

What's even more important though is that the way that clinical events happen, the way heart attacks and strokes occur is that these plaques rupture and they cause an acute occlusion after they rupture. So what statins help do is that they help reduce the inflammatory process, help the plaque heal over and prevent that rupture from occurring. There's different types of 50% blockages There are some 50% blockages that are vulnerable and are more prone to rupturing, and there's some 50% blockages that are quiescent and stable. And statins help convert one type of the vulnerable plaque into the less vulnerable type.

Alyne: Well, thank you very much for this valuable information, Dr. Patrello. It's very encouraging,

Dr. Patrello: Thank you so much for talking with me about this today. It's an extremely important topic that I deal with on an everyday basis. And I think getting information out to community is extremely important.

Alyne: Thank you so much for this valuable information, Dr. Patrello. Dr Anthony Patrello is the Medical Director of the Cardiovascular Institute at Montefiore St. Luke's Cornwall. I'm Alyne Ellis. Thank you for listening to this episode of our Health Track podcast.

Head on over to our website at MontefioreSLC.org for more information and to get connected to one of our providers. And if you found this podcast helpful, please share it on your social channels and be sure to check back in soon for the next podcast. Stay well.