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Interview with Cooper Clinic Head of Cardiology Dr. Nina Radford about Association Between Omega-3 Fatty Acid Supplementation and Risk of Major Cardiovascular Disease Events

September 18, 2012 2 comments

Dr. Nina Radford, Cooper Clinic

Todd Whitthorne talked with Dr. Nina Radford, about the systematic review and meta-analysis Association Between Omega-3 Fatty Acid Supplementation and Risk of Major Cardiovascular Disease Events published in the JAMA September 12, 2012, Vol 308, No 10 issue. Click here if you would prefer to listen to the interview.

Todd:  Hello once again this is Todd Whitthorne with another healthy living podcast and I’m joined today by Dr. Nina Radford, the Head of Cardiology for the Cooper Clinic and we’re going to talk about a recent article in JAMA that discussed a meta-analysis of omega-3 as it relates to the cardiovascular benefits.  So Dr. Radford, this can be a rather complicated topic because we’re talking about statistics and scientific research, but I do know we have a very educated and inquisitive listening audience, so let’s walk through this paper because the headlines we’ve seen in the newspapers or heard on the radio basically came out and said that “omega-3, or fish oil, did not show benefit for cardiovascular health.” Can we dig a little deeper and explain really what this paper was investigating, and what the results showed?

Dr. Radford: Absolutely! I’m just delighted to discuss this with you because as we both know, sometimes these very important papers get condensed into a single, simple sentence or headline that may peak an individual’s attention but doesn’t always tell the whole story…, and this paper I think is a good example of that.

So this paper is a meta-analysis, and what that means is it is combining information from multiple studies, and why would you want to do that? Well, if you combine studies together your population will grow, so for example in this meta-analysis they combined the data from 20 studies so it included almost 69,000 patients.  When you have a larger patient population, it’s easier to see small effects that may occur that may be statistically significant. The problem with combining studies is that all studies are a little bit different… the ages of the patient may be different; the formulation of the omega-3 being used may be different; they time they use the omega-3 may be very different; it may be in a different country where native foods are very different for example, from the United States. So, one of the problems is that when you combine studies that are very different, and you reach conclusions from them, your house is sort of built of rickety wood, so you have to be careful in terms of how you interpret it. That being said, what we have are this combination of 20 studies. The median age is 68, and I’ll remind you median means that 50% or below that age, and 50% are above, and in these studies the age range was 49 to 70. In these studies, the median dose of omega-3 was about a gram, and that’s probably less than most people consider taking daily today.

Todd:  I’m sorry. That’s a gram of EPA plus DHA, not a gram of fish oil, correct?

Dr. Radford: That’s correct. And the range was from .53, so half a gram, which most of us would consider on the lower side, to 1.8 grams per day. The treatment duration was about two years and spanned from one to six, and the important thing about these studies is that 13 of the 20 were secondary prevention studies.  What that means is those participants had already been diagnosed with heart disease. They had heart attack, bypass, heart failure, sudden death, stents, but they were not people who were taking it to prevent the first event. Rather, these were people who were put on fish oil to prevent a second cardiovascular event or death. Four of the studies were mixed primary secondary, you couldn’t really sort out which was which, and three of the studies had to do with preventing sudden death in people who had implantable cardiac defibrillators (those are the internal defibrillators that shock you if you have a potentially life-threatening heart rhythm abnormality). So again, these are patients who are older, they have known heart disease, and they’re taking EPA plus DHA at a median of a gram for about two years.

Now, one of the things that we have to remember in all of this is that there’s pretty good reason to think that fish oil may help when we look at basic science. There have been studies that suggest it lowers blood pressure, lowers triglycerides, may stabilize heart rhythms, may reduce the stickiness of the blood to form to form blood clots, so there’s some good rationale from which these studies were conducted, and that’s always sort of reassuring to know there’s some basic science that underlies these. So in this analysis, they looked at five major outcomes  – all cause mortality (that’s the risk of dying of anything); cardiac death (dying of heart attack); they looked at sudden death (which is a heart rhythm abnormality); rather than having a heart attack and then having heart failure, for example; having a nonfatal heart attack; or stroke.

When we look at whether or not a result is statistically significant, we look at something called the P value, and the P value helps us decide if this result that could happen by chance, or is this the result that can withstand rigorous statistical testing? And we rely on that P value as readers of medical science, to let us know yes, that’s statistically significant, or no it’s not.  We don’t just rely on the number that we see, we have to rely on the statistics to back it up, so in this population is that meaningful.

Now, in most studies that I read, a P value of significance is a P value less than 0.05. When you know that the P value is less than that, you know it’s statistically significant. And when we look at that range of P value in this study, there was actually a demonstrated benefit in terms of reducing cardiac death. It reduced it by about 9 percent. Now, what’s made this somewhat controversial is these authors have decided to make a much more limited P value of .0063, and that’s rather usual, and that requires that the effect be more robust if you will, in order to prove that it’s present.

And when we look at studies – for example you may remember testing hormone replacement, and did hormone replacement reduce the risk of death for example? In all of those studies the P value is 0.05. If you look at whether statin medications reduce the risk of dying from heart disease, the P value is 05. So the use of this very, very small P value, is a little unusual and not everybody is accepting it when we look at this study. So certainly, what I would conclude from this study, based on a P value I think is reasonable, is that there is likely a small reduction in cardiac death in the studies of patients who are older and already had advanced heart disease.

One of the things I think is very interesting in this paper is that they provide sort of a chronologic history. They start with studies done in the mid- 1995’s and they go through the studies that were published more recently in 2012.  And what’s interesting is in the studies that were published in the in the mid-to-late 90s until 2005, there was a benefit of omega-3 in terms of all cause mortality. But when you look at the most recent studies that were published in 2010 or 2012 you did not see that effect. So does that mean that the studies that were done early on were wrong? Absolutely not!  What we see is an effect of improving medical science and improving technology. Compared to 1995, patients who are treated after a heart attack today are treated with much more sophisticated medications. Their lipids are much more aggressively lowered compared to patients in 1995, so if I add a therapy like omega-3 fatty acids, which have a small benefit compared to those other therapies, it may be hard to see that benefit unless you have an extraordinarily large number of patients in the trial. And so, I don’t see this as being a call to throw away all your fish oil.  Rather, I see this as a recommendation that there is likely is benefit, but it’s small, compared to the other known therapies that we have for patients treated after a heart attack.  Now let me be very clear that this has no bearing on patients who haven’t heart disease yet; who haven’t had their first heart attack yet. Maybe they have high cholesterol.  Maybe they have a strong family history of developing heart disease and they want to prevent their first event.  This paper doesn’t address population all.

Todd:  Clearly, what’s interesting about omega-3, is that there are literally thousands of studies that have been done looking at the various and assorted benefits and in a variety of areas, but in particular cardiovascular disease.  So for someone healthy, someone that is just looking to improve their overall cardiovascular risk profile, omega-3 still make sense from your perspective as a cardiologist?

Dr. Radford: I think that they definitely ought to be offered to patients. I think that they definitely may have some benefits in terms of reducing death from cardiovascular disease. I think compared to their other therapies, like statin medications or low dose daily aspirin, that effects may be small, but every little bit helps if we’re talking about reducing your risk of dying of heart disease.

Todd:  And that main benefit as we hear so much about inflammation, that seems to be the benefit of omega-3, as an anti-inflammatory?

Dr. Radford: And there may be benefits well beyond that, that we simply don’t have enough knowledge about.

Todd:  Very good. Well Dr. Radford, as always I appreciate your insight.  It’s like going to Paul Harvey for the rest of the story, to break it down and simplify something that is very, very complex, so we appreciate it.

Folks, if you want more information, you can sign up for The Cooperized Newsletter. As always, we’ll keep you updated with whatever we can here on the podcast and on the website. Until next time, this is Todd Whitthorne. Have a great day. Be healthy.

Interview with Cooper Clinic head of cardiology Dr. Nina Radford about HDL Cholesterol

August 27, 2012 3 comments

Todd Whitthorne recently sat down with Dr. Nina Radford, and discussed HDL Cholesterol. Click here if you would prefer to listen to the interview.

Todd:  Hello, and welcome to another Healthy Living podcast from Cooper Aerobics Center. This is Todd Whitthorne, and I’m joined today by Dr. Nina Radford the head of cardiology at the Cooper Clinic, and Dr. Radford we have a topic today that I think is going to interest a lot of our listeners. Generally when it comes to health, we like to distill things down to takeaways, and when it comes to cholesterol we have a tendency to think that LDL is lousy and the HDL is healthy. There’s a recent study published in May of 2012 in the Lancet that says, well maybe raising HDL is not all that beneficial.  What do we need to know about that?

Dr. Radford: Well Todd, that’s a great question. Historically, when we talk about cholesterol parameters, as you described, we look at LDL, and when it’s high it’s bad for us – it increases the risk of heart attack…, and when we look at HDL, if it’s too low, it increases our risk of heart attack. And those are associations – if we look at a group of people who’ve had heart attacks versus a group of people who haven’t, and you find that high LDL is associated with heart attacks and low HDL is associated with heart attack, but that doesn’t necessarily prove causation.

Now with LDL cholesterol, there have been a number of studies that have gone on from “association” to proving “causation,” and how do we do that? Well first we say “Gosh, if high LDL is associated with heart attack, if we lower it with drugs does that lower the risk?”, and in fact there have been many, many studies showing if you lower LDL cholesterol with diet or medication, you reduce the risk of subsequent heart attacks.

They can also look at from another angle, and that is the genetic angle. There are some people who are actually born with genes that cause their LDL to be low. So, they look in those families who have those genes that cause low LDL, and they ask the question “In those families, is there a reduced risk of having a heart attack?”, and in fact there is. So, whether or not your LDL is low because you take medicine, or you follow specific lifestyles, or it’s low because low LDL happens to run in your family…, either way, both of those situations are associated with a lower risk of heart attack. So you make the transition from “association” to “cause.”

Now investigators are trying to do the same thing with HDL. So we say “Gosh, having a low HDL is associated with heart attacks – having a high HDL must be good for you then!” So we look at studies: If I give you a drug that causes your HDL to increase – something like niacin, for example, will that reduce the risk of having heart? And in fact, there was a recent trial called the Aim-High Trial that took patients who already had a low LDL (so that is they were already on medicine to lower their LDL because they have heart disease), but their HDL was low. Researchers treated patients with a drug that causes the HDL to go and see if it would lower their risk of having another heart event even more! The study did not demonstrate any benefit from increasing the HDL with the medication. So, then all of a sudden, people started to wonder if raising HDL is a good thing, “Is high HDL really protective?” because we didn’t see it in this study. So, what these investigators did in the Lancet study was they looked at people who have a genetic cause of having high HDL – they had genes that ran in their family that actually blessed them with very HDL levels.

Todd:  Dr. Cooper calls that the Methuselah factor. I’ve heard him say that many times.

Dr. Radford: They’re just lucky they were born with a high HDL. Investigators looked at 21,000 people in one study and 12,000 people in another group, so they combined those groups and were looking at over 30,000 individuals who had this gene, and they predicted that the risk of having a heart attack should be lower in these people because they have HDL, and in fact they did not see that the risk was lower.

So here we have this Genetic Study, right on the heels of this Drug Trial, and all a sudden people are saying “Hey, I thought having a high HDL was good for you! What’s going on here?” Well, you have to be careful about dismissing decades of historical data based on a couple of studies.

For example, in this study where they gave a drug to increase the HDL to see if it would reduce risk, well we know that LDL, the bad cholesterol, is a bigger driver of risk than HDL. So if I lower your LDL and get it super low with a drug, plus you’re on an aspirin, and an ACE inhibitor, and fish oil, and you’re meditating, and you’re doing all the right things…, and on top of all those really good things, I add another good thing, it may be that the effect is not big enough that you can see it. Because you’re doing six other good things, and when you add the seventh the benefit isn’t big enough. And so, that may be part of.

But then when you look at this Genetics Study, and you add it to the Drug Study, what’s the story? Well, the story is this: It may be that having a high HDL is a marker for some other thing that you’re doing that’s good. So, for example, we know that if you want to increase your HDL and you exercise, you can do it. But what if exercise causes another thing to happen? So, and I’m going to make it up….. Let’s say exercise increases your “Todd” factor. So, if you’re a regular exerciser, your “Todd” factor goes sky high. Now, your HDL also goes sky high, and we can measure the HDL, but we don’t know how to measure the “Todd” factor.

Todd:  At least not yet!

Dr. Radford: So, it may be that HDL is kind of going along for the ride and the real benefit of exercise is the “Todd” factor that we’re not smart enough to measure yet. So, that’s what we’re not clear about.

Now, should you stop doing things we know will raise HDL? Like being at your ideal body weight, taking some fish oil, exercising regularly? Absolutely not! But whether or not you should take medications to raise your HDL, beyond the other good heart healthy things that you’re doing, is not clear, and what most physicians are doing is taking it on a case-by-case basis.

If you’re taking a medication to raise your HDL don’t stop it, because we’ve only got that one Trial that’s raised some questions…, but it’s a good thing to ask your doctor when you see them next. You’re reviewing all your meds – it’s a good thing to do every year – and say you’re taking this for your blood pressure, taking this for cholesterol, this for prostate, this to make your hair shiny, etc. Every year you’ll want to look at all those meds and talk with your doctor and say “Do I need to take each of these (medications)?” And, if you happen to be on a drug for raising HDL, it’s a good time to review (taking it) and decide if you still need it.

Todd:  So, where are we from your perspective – historically, it’s the question that comes up all the time – “Is at HDL? Is it LDL? Is it the combination, that atherogenic index, of total cholesterol divided by HDL?” Dr. Nina Radford, head of cardiology at the Cooper Clinic, what you think is the most important component? Or, is there a magic number we need to be thinking about, as the average patient?

Dr. Radford: Well, that is a great question! It depends a little bit on what your other risk factors are; what your age is; and what your gender is. So, for example, compared to men, HDL is probably a bigger driver of risk in women. But that has to do with probably differences in our hormones. LDL is still a driver of risk in women – it doesn’t mean you can willy-nilly have your LDL be high and super size your fries, but it looks like some studies suggest in women before they’re had their first heart attack or heart disease HDL is a big driver of risk.

In men, LDL appears to be a bigger driver. When you talk about patients who already had their first heart attack; had a stent; have heart disease…, LDL is a very big driver of risk, and needs to be very specifically controlled.

Todd:  In both men and women?

Dr. Radford: Absolutely! In both genders! So it depends a little bit on the age and the clinical background in terms of which factors I’ll be more concerned about.

Todd:  So the takeaway is case-by-case, patient-by-patient, one size does not fit all?

Dr. Radford: Absolutely.

Todd:  Very good. Dr. Nina Radford, the head of cardiology at Cooper Clinic, great information as always! We appreciate your time Dr. Radford.

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