There have always been people with high LDL who lived to a very old age and finally died of something other than a heart attack (nobody knows why). Still high LDL after controlling for everything we can think of (cholesterol is cheap to measure so we have a lot of data!) is a strong sign of a future heart attack and so anyone with high LDL should talk to their doctor: there is good reason to think statins will reduce your chance of a heart attack. Which why we measure it and control it.
If you have normal cholesterol though - we have long known that people with normal cholesterol also have heart attacks. It isn't as common as people who have high cholesterol, but it is still very common for someone normal cholesterol to have a heart attack. We don't really know what to do about this though. This article is saying we should measure inflammation and if found deal with it. Seems reasonable.
What isn't known is if we deal with inflammation will heart attacks go away or if there are more factors. If there are more factors we don't know what they are or if they are worth measuring/treating (though some researchers may have data they are trying to get out here). If dealing with inflammation is good, can we start ignoring cholesterol - another unknown (one for researchers to look into, but the rest of us should for now say no cholesterol is independently important - until data says otherwise)
LDL is a proxy measure that's cheap and easy to measure. It's widely used for screening despite not being perfect, which confused some into thinking it's the one and only thing measure of CVD risk. It's not, though. Many of the tests we look at are proxies and markers, not actually the sole factor for a disease.
More in-depth testing would check LDL-P (particle count) and ApoB along with hsCRP.
Though realistically, most people could simply look at their diet and lifestyle and work on improving both before investing in any extra testing. The testing can be useful to catch cases where genetics overwhelm even healthy lifestyles, but in many cases for younger people the testing basically serves as a wake-up call to actually do something about lifestyle and diet problems. It's easier to inspire lifestyle and diet changes when you're staring at bad numbers on the test results and getting a little preview of the consequences of your decisions.
My cholesterol is (frankly) through the roof. My GP wanted to start statins immediately. I pushed back and asked what the big deal was -- my RHR is low, BP is normal, my weight is fine, I have an active lifestyle, and my diet is fine. They explained that the cholesterol might build up a blockage in my heart, and that higher levels meant higher increased risk of that. So I asked whether we could just check and see if that's actually happening, and you can! It's a calcium scoring test, and it cost me $150.
I got a zero, in other words, no blockage at all. When I reviewed my results with a cardiologist, he basically said, "Some people just have high cholesterol, and it's not a problem. You're probably one of them." I also separately got tested for the type of LDL particles, and mine were primarily composed of big, floaty ones that aren't associated with increased risk (or at least that's what the test result notes said).
I'll do the calcium score every 5 years just to keep tabs on it. But thankfully I didn't start a needless medication regimen.
Same story here (though it cost me more - insurance refused to cover it because I did not meet the criteria [0])
LDL while clearly not telling the whole story is a great first line defense at population levels because it's easy and cheap (similar to BMI). If you just throw Statins at everybody with high LDL you're going to improve health outcomes, and historically providers and researchers have considered statins to be effectively "free" (both in actual cost and in side effects).
In developed countries where the equipment for this test is readily available, individual patients should absolutely request it even if paying out of pocket, if for nothing more than their own peace of mind.
I'm a layman but I have come to conclude that the AHA's guidelines on when to recommend the CAC test are too conservative. Definitive knowledge of the underlying pathology (or lack thereof) seems like it would be useful both for people with exceptionally high and exceptionally low scores. Even if in a vast majority of cases the treatment plan would be similar (just give them statins) more knowledge seems better on an individual treatment level.
Calcium scores only reflect calcified plaque - not soft plaque. CTTA is what you need for that.
Particularly for people below ~45 with significant plaque buildup, calcium scores are often 0 or very low, because all of the plaque is soft.
This is one of the reasons CACs aren't used much in younger people - that plaque hasn't yet calcified.
Soft plaque is the dangerous stuff, too - most statins actually calcify plaque, but this stabilizes it and prevents it from rupturing and the chunks entering the bloodstream.
You're probably a "lean mass hyper-responders", a phenotype which is actively investigated, initial paper:
Elevated LDL-cholesterol levels among lean mass hyper-responders on low-carbohydrate ketogenic diets deserve urgent clinical attention and further research
Wow, this might actually be me. When I was doing a protein-heavy, carb-light diet, my numbers matched up with these ranges exactly. High LDL, high HDL over 80, and low triglycerides. Granted that was a good 15 years ago, but still. Glad to have something specific to look for.
You're missing a key fact, which others have noted, but I would phrase it differently.
Calcium is the end-stage of atherosclerosis. In other words, only advanced atherosclerosis has calcium. The electron beam CT test can, therefore, read zero in people with extensive atherosclerosis, if it is still in the earlier stages. As others note, even early atherosclerosis is bad.
That is why insurance doesn't cover electron beam CT -- it's a crappy test. It provides no reassurance if it's negative, and on a population scale the LDL is far more cost effective and convenient to identify people who need statins.
You might look back at studies from the early statin days, like AFCAPS/TexCAPS, which looked at healthy people like you, whose only risk factor was high cholesterol. The ones who got even the primitive statins of the day lowered their risk of a first coronary event by 37%. That doesn't even tell the whole story, because atherosclerosis can affect any artery in the body. You want your kidneys, eyes, ears, brain, legs, and penis (when present) to work well to the end of your days. Atherosclerosis is a terrible disease.
LDL is almost always talked about as a singluar thing, even in scientific studies when LDL comes in several flavors.
Large bouyant LDL is not associated with CVD risk whereas small dense LDL is.
You can have high HDL, high LDL and low triglycerides. This is a pretty rare pattern, but one where you do not have increase risk of CVD.
In most people, having high LDL is linked to having high small dense LDL and low aounts of large boyant LDL. Hence why LDL is used as a simple risk measure - even though it's wrong.
Statins in trials show benefits for secondary events, but for primary protection statins don't actually work that well.
This doesn't really seem to pan out in reality. Often people with small dense LDL have it as a result of other risk markers. There's a good discussion here - https://www.youtube.com/watch?v=kplh30RmYo8 - the long and short of it is that when you perform mutual adjustment for number of particles, both large and small LDL particles are associated with a fairly similar risk. But if you have the same mass of cholesterol in two individuals (LDL-c) and one has SD LDL and the other has LB LDL, the latter has fewer LDL particles and therefore lower risk, so it can appear that LB LDL are less risky if you're only measuring cholesterol mass.
As for statins not working well in primary prevention, I'm not sure what you mean - the JUPITER trial showed significant risk reductions for primary prevention, for example.
The Jupiter trial clearly stated that those with low hs-crp didn’t benefit from LDL-C reduction, only those with high hs-crp had reduced CVD events due to LDL-C reduction.
PCSK9 inhibitor trials have shown significant benefit for reduction in CVD events independent of whether or not the inhibitors lowered hsCRP. Ezetimibe makes an impact on events without reducing hsCRP when administered on it's own. (But it is generally administered with a statin, and it seems that the combination does result in lower hsCRP than a statin on it's own)
The claim I was addressing was that we don’t have evidence of statin efficacy for primary prevention. My point was that JUPITER seems to be evidence this isn’t the case.
> Statins in trials show benefits for secondary events, but for primary protection statins don't actually work that well.
This just simply isn't true and we have massive quantities of data pointing towards protection against major vascular events - even in people that we previously would have considered as having "normal" cholesterol. The NLA and AHA has been revising their guidelines to start getting people on statins sooner and to get levels lower for a reason - it works.
> If you have normal cholesterol though - we have long known that people with normal cholesterol also have heart attacks.
Just to continue on this line, we also know that people with a genetic disposition for low cholesterol have a significantly lower risk of coronary heart disease than people with ostensibly normal cholesterol levels. It is one of the most proven, obvious correlations (more cholesterol increases the incident of CHD) in medicine.
Some snake-oil merchants, usually pitching a book or supplement, have often tried to muddy the waters by pointing out that someone at death's door often has very low cholesterol (they usually aren't eating, and cancer often "eats" cholesterol and leads to low levels), trying to then extrapolate this out.
These people with genetically low cholesterol, however, have other issues. Familial hypobetalipoproteinemia (FHBL) is a disorder that impairs the body's ability to absorb and transport fats. Many individuals with FHBL develop an abnormal buildup of fats in the livercalled hepatic steatosis or fatty liver.
You have to understand the point which you’re not yet able to put in your head. Yes it is true that lowering cholesterol lowers cardiovascular disease. No one here is disagreeing with that. What we are explaining is that cholesterol alone does not cause heart disease. It is cholesterol plus inflammation that causes heart disease. I don’t know why this is so hard to understand. Lowering inflammation not only would reduce cardiovascular disease, but also cancer, arthritis and a multitude of other diseases.
> What we are explaining is that cholesterol alone does not cause heart disease. It is cholesterol plus inflammation that causes heart disease.
interesting idea which I have heard before. However so far as I can tell we don't know if it is true. It seems to fit the evidence that the two are independantly causes of heart attack, when combined it is worse.
maybe someday science will figure this out but it is not easy and so will take a while. Until we do I avoid saying things with high confidence.
Cholesterol is more of a proxy "smoke" or "firefighter" measure than a measurement of the actual fire. It's very much a wet streets cause rain kind of thing.
Artificially eliminating the firefighters doesn't necessarily mean you've solved most of the problem.
Heart disease is a far more complicated problem than "cholesterol" or "cholesterol + inflammation", but humans and patients mentally gravitate to silver bullet thinking, which makes it really hard to work with. One interesting measure I've encountered is the lipid clearance rate, but it costs something like +$20k to measure and is not something a doctor can order from a lab; it's typically only performed in research settings.
This isn't necessarily true. High content of certain cholesterols in the blood does cause heart attacks. It doesn't just indicate it - it actually causes it.
And, we have shown the mechanism of action. Certain cholesterols will build up on artery walls, constraining the flow of blood. When there is too much build up and/or the vessel is too narrow, blood can be constrained too much, causing loss of blood flow and therefore oxygenation. The heart has MANY capillaries and requires a lot of oxygen.
Comments like these just aren't based in reality. LDL levels are not a proxy or a wet streets cause rain. We even have a strong understanding of the mechanisms in which cholesterol causes things like heart attacks, strokes, peripheral arterial disease, etc. etc. etc. Something has to deposit plaque in your arteries.
Yes, from a mechanistic standpoint, inflammation is also an important causal factor. Lp(a) is also an important factor for people that are genetically predisposed to high levels - it also deposits plaque, and is one of the reasons ApoB is recommended. Most people don't have worrisome Lp(a) levels but enough do that we've been missing them, and we now also have good treatments for them - PCKS9 inhibitors reduce it by ~1/3rd, and we have Lp(a) specific medications in phase 3 trials that are even stronger.
But we know that statins work. This is some of the most established science in health. I keep seeing claims in these comments from people stating otherwise, but it just doesn't match reality.
We also know that lowering LDL in and of itself lowers inflammation within the arterial wall, though this isn't necessarily reflected in hsCRP. We know that foam cell activation and cytokine signaling increase inflammation at the site of the plaque, which results in further deposition, and these require ApoB particles be depositing plaque there to begin with. Some PCSK9 inhibitors show zero change in hsCRP results yet still show less localized inflammation - due to the significant reduction in LDL-C and Lp(a) particles.
Lowering inflammation also works for reducing events independent of lowering ApoB particles - colchicine works even though it does nothing there - but if we're really trying to stretch the fire analogy, it's more like LDL and Lp(a) are the years of unmaintained brush and flammable debris in a forest, and inflammation is the strong winds. Both can lead to the spread of fire even without the other, fire can still spread even in the absence of both, but having either and especially having both will greatly increase the risk of the fire continuing to spread.
>These people with genetically low cholesterol, however, have other issues
Neat.
>You have to understand the point which you’re not yet able to put in your head
Nowhere did I ever dismiss other causative inputs. All I did was reply to some probably-listen-to-chiropractor people who sure are trying incredibly hard to downplay cholesterol.
If one person with high cholesterol does not get heart disease then cholesterol is not the problem. Fact. Logic.
Why don’t you stop your appeal to authority arguments and focus on the facts.
It’s not that I haven’t died yet either. My calcium artery score was zero. I have no plaque in my arteries and I’ve had high cholesterol for probably 30 years of my life because of my genetics.
If that is not interesting to you then you have an odd bias. I merely saying that inflammation is the risk factor that matters more than high cholesterol. You can lower cholesterol for someone who has high inflammation and reduce heart disease, but reducing inflammation is more important overall.
>If one person with high cholesterol does not get heart disease then cholesterol is not the problem. Fact. Logic.
This is such a silly statement I'm not sure where to begin. Plenty of people smoke and drink and don't die of issues related to smoking or drinking, but smoking and drinking are bad for you.
Individual response to things varies. No one reasonable is going to say that because such and such person did X, Y, Z things that we know are bad and didn't have a negative outcome that we must flip the script on if those things are bad are not. Exceptions exist for a wide variety of reasons.
> It’s not that I haven’t died yet either. My calcium artery score was zero. I have no plaque in my arteries and I’ve had high cholesterol for probably 30 years of my life because of my genetics.
Calcium score does not tell you how much plaque you have in your arteries - it tells you how much calcified plaque you have in your arteries. This is NOT the same thing. You need a CCTA to tell if you have soft plaque or not.
I'm sorry, but you're just severely misinformed here and spreading all sorts of dangerous misinformation all over the comments here.
> The body does not need cancer, but it does need LDL to transport fats around the body.
Of course the body needs cancer.
Cancer is your own bodies cells. They're essential for you being alive. And, cells with damaged DNA train and hone your immune system.
You have millions of cancer cells in your body right now. Your immune system is killing them as we speak.
If a few happen to slip through, then that's we would say you have cancer. Why might they slip through? Your immune system makes mistakes. Because everything makes mistakes.
> What was it that he did that proved him immune to the ravages of smoking?
Um, nothing?
Is this your first day on Earth? Life is not an algorithm.
Everything is risk, everything is probability. Smoking increases your risk. It doesn't give you anything.
Your HIV and AIDS argument is just fucking stupid. Sorry to be blunt.
Yes, SOME things are A -> B. That is an extremely rare exception to the rule. Extremely. That almost never happens.
Like, if I drive fast, I might die. Might. Its not a garuantee.
I can drive 150 every day and live, or drive 10 and die immediately. That's life. Welcome to risk and probability. That's just how things work.
Having LDL and no heart disease doesn't prove anything to anyone. That doesn't prove LDL doesn't cause heart disease.
If you have normal cholesterol though - we have long known that people with normal cholesterol also have heart attacks. It isn't as common as people who have high cholesterol, but it is still very common for someone normal cholesterol to have a heart attack. We don't really know what to do about this though. This article is saying we should measure inflammation and if found deal with it. Seems reasonable.
What isn't known is if we deal with inflammation will heart attacks go away or if there are more factors. If there are more factors we don't know what they are or if they are worth measuring/treating (though some researchers may have data they are trying to get out here). If dealing with inflammation is good, can we start ignoring cholesterol - another unknown (one for researchers to look into, but the rest of us should for now say no cholesterol is independently important - until data says otherwise)