are ratios like total cholesterol over HDL-cholesterol or triglycerides over
HDL-cholesterol the best measure of our risk of heart disease? we've talked about these ratios
several times in the past but this is such a common question,
it comes up almost daily in the comments, that I thought it deserved its own video. it's
widely known that these ratios correlate with cardiovascular disease in population studies,
in epidemiological studies. so if we take a population of, say, a hundred thousand people,
these ratios will associate with the likelihood of having heart attacks. but lots of things
correlate with risk and are predictive of risk but don't actually cause risk. the example we
gave last time was that carrying a lighter with us probably correlates with disease. lung cancer
and heart disease. in average, the subset of the population that carries a lighter with
them all day is going to be sicker than people who never carry a lighter. in average, right?
but carrying the lighter doesn't cause disease. it's a marker of something else. similarly, these
metrics that people use for the ratios (total cholesterol, HDL-cholesterol, triglycerides),
they correlate with risk, they're markers of risk, but they don't actually cause risk.
total cholesterol for example is a marker of the lipoproteins that cause cardiovascular disease,
the so-called ApoB lipoproteins. triglycerides are a marker of things like obesity, diabetes, insulin
resistance, among others. and HDL-cholesterol is a marker of a number of things including obesity,
diabetes, liver disease, smoking etc etc etc. but these metrics don't actually cause any risk,
and we know that from several lines of evidence including randomized controlled trials and genetic
data. we've actually gone over all of this in previous videos and I'll link some of those
below for people who want more detail, going over the evidence step by step, today we're focusing
on this ratios question. so take HDL-cholesterol, for example. in epidemiological studies, people
who have higher HDL-cholesterol tend to have lower risks of heart disease, because it reflects all
these other factors, but people who have high HDL-cholesterol determined genetically aren't
protected and raising HDL-cholesterol directly with a drug in randomized trials, for example,
doesn't help either. so because of that body of evidence, it's generally well accepted now in
cardiovascular research that HDL-cholesterol doesn't lower risk per se. it's a marker of
something else, it's a reflection of something else. so what is actually protective? what does
lower risk causally? glucose level, smoking, ApoB, blood pressure. there's a few others but
this type of factors do appear to modulate risk directly, causally, because if you lower them in
somebody in a clinical trial, for example, or if you look at genetically determined levels,
then risk is changed, unlike some of those other metrics we looked at. okay, back to the ratios,
triglycerides and HDL-cholesterol both correlate with risk in these epidemiological studies, so
of course a ratio that combines them is going to correlate with risk pretty well also. but it can
sometimes be falsely reassuring to look only at those ratios, because for example HDL-cholesterol
can change and make the ratios look better but, as we saw, not necessarily do anything to risk. I
recently got the chance to chat with the president of the European atherosclerosis Society, Professor
kausik ray, and I brought up this exact question of the ratios, we briefly touched on it in our
conversation, so here's what he said. what about the ratios? people ask about this... don´t use the
ratios. don't use the ratios, period. that fact that I was telling you about, the HDL-cholesterol
being no more protective, so think, if you use the ratio, the ratio basically is flawed.
because if the HDL-cholesterol is raised the ratio looks better but the risk hasn't budged? exactly,
exactly. okay, okay. ok but it's still confusing, because how can something correlate well with risk
in a population setting and yet be unreliable? it just feels intuitively like something that
is a good predictor populationally should also be a good metric for me to assess my personal
risk of heart disease, right? it just feels like it should be true. if we go back to the
lighter analogy, people who carry lighters tend to be sicker than people who don't, in average.
we can immediately see how that breaks down at individual level. some smokers don't carry
lighters. maybe they use matches or something. and someone might carry a lighter for some other
reason and not smoke. so the lighter is an imperfect marker that shows a correlation
in a populational average but is not reliable one to one for each individual person. we can
be way off. and if we take the analogy one step further and we add a second marker to the lighter,
so having a gym membership, right? as a marker of being physically active. and if I look at both of
those combined, maybe I come up with a ratio of lighter-carrying to gym membership-owning,
it'll probably be a decent predictor of disease risk in a population, and it'll be better than
each of those markers in isolation. and actually this ratio might even be more predictive
than an actual cause of disease like smoking, because the lighter is an imperfect marker of
the smoking habit as we saw but it probably does overlap with smoking most of the time,
70 or 80% of the time people who carry lighters are going to be smokers and most smokers are going
to carry lighters. and if the gym membership overlaps with Physically Active people
sixty percent of the time, then having both of these markers combined in this ratio
might actually be a better predictor than just smoking, even though each one of the markers alone
is imperfect, because we're capturing several risk factors instead of one. but if I turned and
said to you, I smoke like a chimney and I never exercise, I'm very sedentary, but I never carry
a lighter anywhere, I got rid of all my lighters, and I have a full-time gym membership. I never go
but if you go to the gym and check, it's there, I'm paying it in full. so my ratio, my lighter
to gym membership ratio, is stellar, and that looks really good in epidemiological studies,
it's a really good predictor, so I'm not worried about my smoking and my lack of exercise, I'm
not looking at that, I'm just looking at the ratio which is a better predictor in these observational
studies. you can immediately see the flaw in that logic, nobody's confused by that, and yet I see
influencers suggesting exactly this logic all the time. the triglycerides to HDL-cholesterol ratio
is a great predictor in epidemiological studies so don't worry about your high ApoB, don't even
look at it, pretend it doesn't exist, just look at your ratio because it's the best observational
predictor. huge mistake. you're ignoring causes to focus on imperfect Reflections. so that's how
something can correlate well in a population and be a good predictor, right? and yet break down at
an individual level and not be reliable. these ratios can reflect positive changes like weight
loss, for example, but having a good ratio doesn't guarantee lower risk because the components,
those metrics used in the ratios, can change without risk necessarily changing, because
they're not causal. so these ratios never replace causal factors like glucose, blood pressure, ApoB,
smoking etc etc. that's the take-home message. oh, real quick, people often also ask about ApoA-I
ratios, like ApoB divided by apoA-I for example, and it's very similar to the ratios we just looked
at because ApoA-I actually tracks pretty well with HDL-cholesterol and ApoA-I also
doesn't appear to be causal in the same lines of evidence. so it´s an identical situation,
ApoA-I can change, making the ratios look better or worse, while risk doesn't necessarily change.
this is not the easiest topic to clarify so we'll keep revisiting this in the future and every time
I get the chance to talk to one of these leading cardiovascular researchers I'll try to ask them
their take so we can all keep learning. I'll also link below in the description some of our
previous content on ApoB and all this causality story and all those studies for people who want
more detail. let me know your questions below, thanks for watching, I'll see you next time, bye