[Rhonda]: Do you think that statins are overprescribed in a way based on, you know, the fact that
most physicians don't look at all the LDL particle sizes, don't look at all the genetic
factors?
They just look at, you know, total LDL cholesterol, and it gets really high.
You know, maybe they have high ApoB, they may prescribe statins, you know.
Whereas if you look at two people, they may both have high LDL total cholesterol, but
one may have no small, dense LDL, and one may have high.
So, and then what about the side effects of statins?
So, are they overprescribed?
And are there side effects?
[Ron]: Okay, these are great questions which have a lot of implications.
Regarding the prescription of statins, depending on which hat I choose to wear.
I could argue that statins are overprescribed because a lot of people are taking statins
who are not likely to benefit.
But I can put on another hat and say there's a lot of people out there who should be on
statins who aren't because physicians aren't really sufficiently aggressive in taking high-risk
patients and lowering their LDL in a way that still is safe.
So there are subsets of the population that are undertreated and there's a large segment
of the population who are taking statins prophylactically based on guidelines which have continued to
evolve, which I was part of that process for a while, and then I withdrew from it because
I realized I was not happy with the way things were going in terms of the recommendations,
which have evolved to identify even larger segments of the population that should be
taking statins to the point that, I think, there are a huge number of people that are
going to be taking statins who really don't need it.
And that's where the adverse effect problem comes into play.
So my current NIH grant, which is, again, the biggest part of my program right now,
is to identify markers for susceptibility, both to the benefits of statin as well as
to the adverse effects.
Some of those adverse effects, people tend to minimize because the benefits for high-risk
patients are so evident from the clinical trials.
But as you look at the data, there are some pretty surprisingly adverse things that are
out there that are a little bit below the radar screen.
One of them is muscle effects, which surely have been recognized.
People tend to think about them in the more extreme case where people get muscle damage
and life-threatening complications of muscle breakdown.
That's very rare, fortunately.
Otherwise, statins wouldn't be out there in the way they are.
But we and others need to develop evidence that there may be effects on muscle metabolism
that might be much more widespread that could accumulate over time in a way that may not
be manifested in an obvious symptom, but could lead to changes in muscle function, muscle
strength.
This is a hypothesis that I know has worked in between now in terms of the adverse effects
of statins on muscle.
But there is an even bigger problem, which emerged a few years ago, from one of my colleagues,
actually, at Harvard who discovered in a clinical trial that he organized and then it turned
out to be in the literature, people just hadn't really recognized it.
A significant percentage of people taking statins go on to develop diabetes, and diabetes
is not something you want to acquire as a result of drug treatment.
It, of course, increases heart disease risk.
The magnitude of that effect turns out to be surprisingly high.
It's something on the order of 11% to 12% of statin users are at risk for developing
type 2 diabetes.
In women, in particular, we published a paper that sort of opened this up, actually.
In women, the evidence is maybe 2 or 3 or 4 times that, maybe as many as 30% to 40%
of otherwise healthy women who are put on statins could go on to develop type 2 diabetes
over time.
That's a very unacceptable number.
Now, if you're a woman that has a high LDL or a woman that has a predisposition to heart
disease risk, that shouldn't stand in the way of treatment.
But because our guidelines have opened up statin use to a much larger percentage of
the population as a prophylactic, in what was called primary prevention that is in healthy
people who have not yet had a risk of heart disease, but who are considered at risk, because
a high percentage of those individuals, and women, I would point out in particular, have
a relatively higher likelihood of an adverse effect, type 2 diabetes in particular, than
benefit.
I think we have to look seriously at finding ways of improving our selection of patients
for statin use, and that, again, is driving my research.
And fortunately, again, as much as I'm wedded to nutrition and its role in health, and in
heart disease in particular, statins are a lot easier to study.
And I think, from the public health standpoint, especially now with widespread use of statins,
almost like a dietary supplement that people take statins, you know, so it's like a vitamin,
we have to be really careful about that.
And that's where, I think, hopefully, the studies we're embarking on, and this year,
in the current phase of our grant cycle, we're just starting to do this, where I really feel
very committed and passionate about using the tools of what we call precision medicine
or genomic medicine as well as more refined laboratory tools such as particle measurements,
I'll come to that in a minute, to better identify those people who are most likely to benefit.
So I think physicians, getting back to your question, who are using LDL cholesterol as
the barometer of statin efficacy are potentially going in the wrong direction.
And we need better attention to the particles and the measurements of the particles themselves
rather than LDL cholesterol.
When we, as physicians, are recommending, particularly drug treatment, we should be
monitoring those particles as a primary target of treatment because they are, and particularly
smaller particles give us a much better handle on therapeutic benefit of any treatment.