How do statins work?

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helli said:
How do you know if you are taking "longer acting" or "shorter acting" statins?
There is no hint on my packaging about how fast acting mine are.
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Short-acting statins work better at night because the liver enzyme that produces cholesterol is more active at this time. Most short-acting statins have a half-life of 6 hours. A medication’s half-life is the time that it takes for the body to process and remove half of the medication.

Short-acting statins include:

  • lovastatin (Mevacor)
  • fluvastatin (the standard-release tablet)
  • pravastatin (Pravachol)
  • simvastatin (Zocor)

Long-acting statins​

It takes longer for the body to process long-acting statins, which may have a half-life of up to 19 hours.

The two reviews above noted that long-acting statins worked equally well whether a person took them in the morning or the evening. Therefore, people taking long-acting statins can choose which time of the day best suits them.

The authors recommend that people using long-acting statins take them at a time of day that is easy for them to remember. It is important to be consistent with the timing of doses, so if a person prefers to take statins in the morning, they should take them in the morning every day.

Long-acting statins include:

 
Eddy Edson said:
The new US risk calculator is more nuanced: https://professional.heart.org/en/guidelines-and-statements/prevent-calculator

Better focus on the "cardio-renal" profile: considers both eFGR and (optionally) uACR. Considers HbA1c level. For younger folk produces a 30 year assessment, more useful than just10 years except for people who don't intend living longer than 10 years 🙂. Stratifies by baseline non-HDL-C, not the discredited total chol/HDL ratio used by QRISK.

Units are in American, of course, but easy enough to convert. Obviously referenced to a different population compared to the UK, which presumably limits usefulness to some extent.

If you know your CAC, there's another useful professional calculator which adds that into the mix: https://internal.mesa-nhlbi.org/about/procedures/tools/mesa-score-risk-calculator
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Many thanks for these - will definitely investigate. Just the fact that it uses non-HDL cholesterol instead of a ratio is a good sign.

On CAC - am I correct that this is a measure of how far progressed atherosclerosis is in a person? That it involves some kind of somewhat expensive scan, and so is not offered to people unless they have been diagnosed with some kind of cardiovascular problem? If it was free I'd get the test done, but if it costs significant money to get it done privately I assume just setting a fairly low target for non-HDL is probably good enough for most people?
 
Wendal said:
Short-acting statins work better at night because the liver enzyme that produces cholesterol is more active at this time. Most short-acting statins have a half-life of 6 hours. A medication’s half-life is the time that it takes for the body to process and remove half of the medication.

Short-acting statins include:

  • lovastatin (Mevacor)
  • fluvastatin (the standard-release tablet)
  • pravastatin (Pravachol)
  • simvastatin (Zocor)

Long-acting statins​

It takes longer for the body to process long-acting statins, which may have a half-life of up to 19 hours.

The two reviews above noted that long-acting statins worked equally well whether a person took them in the morning or the evening. Therefore, people taking long-acting statins can choose which time of the day best suits them.

The authors recommend that people using long-acting statins take them at a time of day that is easy for them to remember. It is important to be consistent with the timing of doses, so if a person prefers to take statins in the morning, they should take them in the morning every day.

Long-acting statins include:

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Well there you go, I never realized there were two types.
Useful info thanks
 
Tdm said:
Shes not a medical doctor and doesn't seem to have any research experience beyond a phd...pretty low level stuff.
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would love a degree never mind a phd
 
Satan’s little helper said:
Took a watch of this last night. The Doc said something along the lines of statins working partly as an “ani-inflammatory. So why not the use of aspirin?
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I thoroughly enjoyed the conversation and looking at the number of likes and comments so did thousands of others.

Yes, he made the point about it being not so much the LDL lowering function of statins (statins that originally only provided this effect were shown to have few noticeable benefits on life expectancy) but instead, the newer statins that also reduce inflammation had much more profound health benefits.

He also pointed out that insulin resistance is one of many causes of inflammation of cells, so if one has insulin resistance, we can see why they would benefit from statins.

Yes, your comment on the anti-inflammatory functions of aspirin is a good point too.


The Anti-Inflammatory Effects of Statins on Coronary Artery Disease: An Updated Review of the Literature - PMC

Statins have long been used for the protection against coronary artery disease (CAD). Their beneficial effect apart from cholesterol reduction lies in their pleiotropic properties. Emerging evidence from laboratory studies and clinical trials as ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
 
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Amity Island said:
I thoroughly enjoyed the conversation and looking at the number of likes and comments so did thousands of others.

Yes, he made the point about it being not so much the LDL lowering function of statins (statins that originally only provided this effect were shown to have few noticeable benefits on life expectancy) but instead, the newer statins that also reduce inflammation had much more profound health benefits.

He also pointed out that insulin resistance is one of many causes of inflammation of cells, so if one has insulin resistance, we can see why they would benefit from statins.

Yes, your comment on the anti-inflammatory functions of aspirin is a good point too.


The Anti-Inflammatory Effects of Statins on Coronary Artery Disease: An Updated Review of the Literature - PMC

Statins have long been used for the protection against coronary artery disease (CAD). Their beneficial effect apart from cholesterol reduction lies in their pleiotropic properties. Emerging evidence from laboratory studies and clinical trials as ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Let’s just say I had a relative have a mild stroke many years back? They were told to take aspirin. (As a further preventative of recurrence.) This pricked up my ears on the video. Now. I rarely need pain killers. But neither do I need Potential reported joint pain or fog brain from the reports of statins? I still got a few years work in me before I can even think about “retirement.” 🙂
 
PerSpinasAdAstra said:
QRisk 3 is a blunt instrument alright, though I suppose they'd need a huge amount of data to improve it.

Example: Diabetes - None, Type 1 or Type 2. No accounting for HbA1c, time since diagnosis or anything like that. As a result there are some who don't trust it, believe that being in remission means they are free of increased risk of heart disease (despite insulin resistance being a risk factor, despite having spent years progressing from healthy glucose levels all the way to a T2 diagnosis) and believe that their doctor is engaged in a box-ticking exercise by suggesting a statin. It's a problem, though on the diabetes question alone they'd need a massive amount of data to make the calculator better and it would be more complex to use.

Smoker: For me, I'm 'ex-smoker'. There's a world of difference between a person who smoked 10 a week for a couple of years and a person who smoked 20 a day for 20 years. The calculator treats both scenarios the same. Far from ideal, but it is what it is I suppose.
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Bottom line is nobody knows what if being in remission, even long term, means in terms of cardiac risk. There is research going on now, but that is still small scale, but that's how it all tends to work.

Small study shown "more work required". If sexy, or potentially profitable enough, larger scale research studies are supported and so it goes on.

Until a few years ago, "remission" (by whatever definition you choose) wasn't considered, never mind investigated.
 
PerSpinasAdAstra said:
Many thanks for these - will definitely investigate. Just the fact that it uses non-HDL cholesterol instead of a ratio is a good sign.

On CAC - am I correct that this is a measure of how far progressed atherosclerosis is in a person? That it involves some kind of somewhat expensive scan, and so is not offered to people unless they have been diagnosed with some kind of cardiovascular problem? If it was free I'd get the test done, but if it costs significant money to get it done privately I assume just setting a fairly low target for non-HDL is probably good enough for most people?
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I don't know what the NICE guidelines say about coronary calcium screening, but in general it might be most useful for up- or down-staging people who are at intermediate risk according to the standard calculators.

FWIW, for CVD things I follow AHA guidance which I think is usually more robust & current with a richer available discussion of the evidence base. This is what the latest CVD primary prevention guidance has to say:

For individuals with intermediate predicted risk (≥7.5% to <20%) by the PCE [pooled cohort equations; predecessor to the new PREVENT equations] or for select adults with borderline (5% to <7.5%) predicted risk, coronary artery calcium measurement can be a useful tool in refining risk assessment for preventive interventions (eg, statin therapy).S2.2-4 In these groups, coronary artery calcium measurement can reclassify risk upward (particularly if coronary artery calcium score is ≥100 Agatston units (AU) or ≥75th age/sex/race percentile) or downward (if coronary artery calcium is zero) in a significant proportion of individuals.S2.2-15 The extent of reclassification is sufficient to provide confidence that borderline- or intermediate-risk patients with elevated coronary artery calcium will have event rates that clearly exceed benefit thresholds (ie, ≥7.5% in 10 years) and those with coronary artery calcium scores of zero will have event rates <7.5%, which can help guide shared decision-making about statinsS2.2-15,S2.2-16,S2.2-21 or potentially even aspirin.S2.2-70 In observational data, the presence and severity of coronary artery calcium have been shown to be associated with the likelihood of benefit from statin therapy for ASCVD risk reduction.S2.2-71 Coronary artery calcium scoring has superior discrimination and risk reclassification as compared with other subclinical imaging markers or biomarkers.
In the MESA (Multi-Ethnic Study of Atherosclerosis) trial, the coronary artery calcium score was strongly associated with 10-year ASCVD risk in a graded manner across age, sex, and racial/ethnic groups, independent of traditional risk factors.S2.2-17 Coronary artery calcium may even refine ASCVD risk estimates among lower-risk women (<7.5% 10-year risk),S2.2-7 younger adults (<45 years of age),S2.2-20 and older adults (≥75 years of age),S2.2-26 but more data are needed to support its use in these subgroups. A coronary artery calcium score of zero identifies individuals at lower risk of ASCVD events and death over a ≥10-year period,S2.2-15,S2.2-17,S2.2-25 who appear to derive little or no benefit from statins for ASCVD risk reduction.S2.2-71 Thus, the absence of coronary artery calcium could reclassify a patient downward into a lower risk group in which preventive interventions (eg, statins) could be postponed.S2.2-22

Note that the absence of coronary artery calcium does not rule out noncalcified plaque, and clinical judgment about risk should prevail. Coronary artery calcium might also be considered in refining risk for selected low-risk adults (<5% 10-year risk), such as those with a strong family history of premature coronary heart disease (CHD).S2.2-23 MESAS2.2-28 and Astro-CHARM (Astronaut Cardiovascular Health and Risk Modification)S2.2-29 are risk estimation tools that incorporate both risk factors and coronary artery calcium for estimating 10-year CHD and ASCVD risk, respectively. Coronary artery calcium measurement is not intended as a “screening” test for all but rather may be used as a decision aid in select adults to facilitate the clinician–patient risk discussion.

 
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JITR said:

An Examination of the Cholesterol Hypothesis​

This recently updated article seems to me a fair assessment of the state of play in the statins debate, at least to me as a bystander.

Would you agree?

https://www.verywellhealth.com/is-the-cholesterol-hypothesis-obsolete-4136732
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Clicked the link, started reading, came to this section:

​

" Non-Statin Therapies​


Some studies found substantially lowered LDL cholesterol levels with non-statin therapies. However, they did not show improved cardiovascular outcomes.

Treatments used in these studies included:

Indeed, despite improved cholesterol levels in some of these trials, a substantially worse cardiovascular outcome was seen with treatment."

*******************************

I thought - this can't be true... I'll pick Ezetimibe, because I know a little about that one. I looked for some kind of research overview, and found this paper - Link

It seems that Ezetimibe, by itself, hasn't been proven conclusively in clinical trials as a standalone drug to improve cardiovascular health outcomes. When added to a low-dose statin though, it has indeed been shown to improve outcomes. Statin + Ezetimibe is better than statin alone. If the text of the article is correct, that only statins have the magic power to prevent heart attacks, and that it's not about cholesterol levels themselves, then how would Ezetimibe help? How would adding a mild cholesterol-lowering medication to a more potent one make any difference, unless it actually is all about the cholesterol? Bear in mind, Ezetimibe alone has less of an effect on LDL than a statin - the clinical trial to show a statistically significant change in health outcomes due to Ezetimibe alone would take years longer than a statin trial. However...

There is a reason the newer medications don't have the same level of clinical trial data to back them up in the same way that statins do, and it is this: A clinical trial for a single cholesterol medication involves getting a large group of people to take that one medication, and another group to take a placebo. If the people you are studying have high cholesterol levels, or are at high risk for other reasons, asking them to stop their statin for years and take a placebo instead is unethical, given the present state of scientific knowledge. People in the placebo group would die. If the new medication being tested didn't work very well, people in the treatment group would die too. New medications can't ethically be tested in the same way as statins could back in the day. They are typically tested along with a statin. That means far fewer new trials of the original statin kind, and fuzzier data from the mixed-drug trials.

The text quoted above from the article is highly misleading. I've only checked one medication on the list and it did indeed show improved outcomes. The article fails to mention why it is common to do trials with medications on top of statins, rather than as individual treatments. I'm also aware of another way to demonstrate issues with that article. Very many quite recent studies have matched ApoB levels (more or less equivalent to LDL cholesterol, which were studied a whole lot in the 70s, 80s and 90s) to cardiovascular risk and all-cause mortality directly - like this recent one from China which isn't behind a paywall - Link. Nobody is trying to prove that cholesterol causes heart attacks any more - that's old news, for decades now. This recent Chinese study about whether ApoB is a better indicator than LDL, and whether higher death rates seen at very low cholesterol levels are due to malnutrition, which, it seems, they are.

Independent of any drug clinical trial it's been shown that people with high cholesterol tend to die younger than people who don't, so long as they're well-fed. On a graph, there's a clear correlation every time. Studies a bit like this one but which were conducted in the late 70s and early 80s are why statins were developed in the first place. The scientists saw these correlations, the drug companies spent the money to develop a drug to lower cholesterol, and it worked as expected. Proven in a great many clinical trials to save lives. Did the pharma companies accidentally develop a drug that prevents heart attacks by some other mysterious means, while what they really wanted to do was develop a drug that prevents heart attacks by exactly the mechanism that they set out to achieve? By lowering cholesterol? Like the scientists said it would before the billions of dollars were spent developing the drugs?

Perhaps not the best 'health' website in the world that one.
 
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In my various readings, verywellhealth.com has always provided less good / less detailed information than some other sites, but last night I was severely lacking in energy and motivation to post (or do anything).

verywellhealth quote says "Experts are questioning the cholesterol hypothesis. That’s because studies have found that non-statin therapies alone have not improved outcomes. It has been considered that statins’ other effects on the body may play a role in their clinical benefit." and that "These other effects stabilize atherosclerotic plaques and could explain much of the clinical benefit seen with statins"

My first issue with this article was the inclusion of Niacin. If prescribed to treat cholesterol it needs to be in such a high dose that it can have adverse effects on health. Consequently it's not something that is really used for cholesterol, so why even have it in the list?

Basically the basis of comparing statins and non-statins seems flawed to me. It's like comparing apples with oranges, both fruits, but they have different qualities. If comparing them as standalone medicines (rather than a statin plus a non-statin) then the comparison should be
a) statin
b) non-statin plus lifestyle modifications

HDL cholesterol helps remove other forms of cholesterol from your bloodstream. Higher levels of HDL cholesterol are associated with a lower risk of heart disease. As discussed by the Mayo clinic

Harvard health discusses lifestyle changes to reduce vascular plaque build-up, which is basically
Eating a Mediterranean diet
Quitting smoking, and Exercising. Both of which can help raise HDL levels

verywellhealth quote says " Some questions experts are considering include:
* Why do some people with high LDL cholesterol levels never develop significant atherosclerosis?
* Why do some people with “normal” LDL cholesterol levels have widespread cholesterol-filled atherosclerotic plaques?
* Why does lowering LDL cholesterol levels with one drug improve outcomes, while lowering LDL levels with another drug does not? "

We could just as easily ask why oats cause a big BG spike in one person, but not in another?
Why does a specific diabetes medication make one person feel ill, but not another?
We are all different, and our bodies process food and medication differently, and it would seem they handle cholesterol differently.
 
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s'nic said:
If comparing them as standalone medicines (rather than a statin plus a non-statin) then the comparison should be
a) statin
b) non-statin plus lifestyle modifications
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Why the suggestion of standalone statins rather than statins with lifestyle modifications (where possible)?
Perhaps the study should include a third category.

s'nic said:
"Some questions experts are considering include:
* Why do some people with high LDL cholesterol levels never develop significant atherosclerosis?
* Why do some people with “normal” LDL cholesterol levels have widespread cholesterol-filled atherosclerotic plaques?
* Why does lowering LDL cholesterol levels with one drug improve outcomes, while lowering LDL levels with another drug does not?"
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And whether those who have high LDL but never experience significant atherosclerosis are those who have what is considered to be a "healthy lifestyle".
It seems to be that all studies about the benefits of statins and risks of high LDL are done with people who are overweight or smokers or rarely exercise or eat a diet high in saturated fats.
What about those of us who have (for want of a better phrase) "genetically high LDL" despite their lifestyle. Are we equally likely to experience significant atherosclerosis or is the high LDL a red herring?
 
@helli I put standalone statins in my example because the article made a point that statins reduced cardiovasular risk, but non statins did not. If they had included a cardiovascular risk strategy in conjunction with the non-statins, then a comparison may have shown less of a difference in performance (of course lifestyle modification does mean the patient has to be fully engaged in changing their health)

Oop, I forgot the quotes, it was their words i was querying. I shall edit.
I just feel the article is flawed in it's composition and the addressing of differences
 
helli said:
And whether those who have high LDL but never experience significant atherosclerosis are those who have what is considered to be a "healthy lifestyle".
It seems to be that all studies about the benefits of statins and risks of high LDL are done with people who are overweight or smokers or rarely exercise or eat a diet high in saturated fats.
What about those of us who have (for want of a better phrase) "genetically high LDL" despite their lifestyle. Are we equally likely to experience significant atherosclerosis or is the high LDL a red herring?
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The clinical trials are done on people who have known elevated risk. The reason is that a trial in that kind of group can be expected to achieve quicker results, which means a cheaper trial and one that enables a pharma company to get their drug to market sooner.

Genetically high LDL is definitely a risk in extreme instances - people with familial hypercholesterolemia, if untreated, die young of heart attacks pretty much regardless of lifestyle (though I would guess that does make a difference).

Outside of the extremes the data mostly comes from large population studies like the one from China I linked above. Having higher LDL is associated with a higher risk of heart attacks, strokes and death - the higher it is the worse it is, when looking at large groups. People of average LDL aren't typically prescribed a statin at a relatively young age but are certainly not immune to dying of a heart attack - they're just not at especially high risk, on average. Heart disease is the biggest killer in the world and so at a global scale there are vast numbers of people dying of heart attacks without having had especially high LDL all their lives. I would imagine though that the great majority of those had other risk factors.

Some people have been shown to have high LDL all their lives and have no sign of atherosclerosis. The reason is unknown but thought to be probably genetic. It's either genetic or there is some factor out there which can prevent heart disease which has yet to be identified. Given all the studies looking at food and smoking and exercise and such I'm not sure what that might be other than some sort of genetic resilience. It certainly seems that some people have a long family history of heart attacks which perhaps indicates the opposite; a genetic susceptibility.

So you could say that if you're looking at large groups, LDL is not a red herring. When looking at individuals the science isn't at a point where all the possible factors can be taken into account. On an individual level, for a person who has been around a few years, the Coronary Artery Calcium (CAC) test mentioned somewhere up the thread might be the best indicator. It tests for existing atherosclerosis. If the result is zero, entirely clear arteries, despite a lifetime of quite high LDL levels, that to me sounds like a strong indicator of very good lifestyle and genetics. Without that test nobody really has a clue though - all we have is the kind of information described above.
 
helli said:
After a decade of declining the kind offer of statins, and my cholesterol creeping very very very slowly up, I decided to give them a go. My idea is to try them for 3 months and then decide whether I have any side effects and whether the benefit outweighs them. All I was told was "they will reduce your cholesterol and chance of having a heart attack".
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@helli
Your question interested me. Knowing little or nothing about cholesterol or statins, I wanted to confirm my choice not to start taking statins again after losing enough weight to reverse my fatty liver and my T2D.

The statistics of large meta analyses certainly tell us statins "will reduce your cholesterol and chance of having a heart attack". Simple as that. The mechanism for lowering cholesterol seems to be that statins inhibit our natural production of cholesterol, thus offseting any increase due ingestion of cholesterol in food.

However this is a bit like trying to predict our local weather from the long range weather forecast. The authorities are interested in the overall and individual departures from the average do not matter provided the average is moving in the right direction.

The question is why your "cholesterol creeping very very very slowly up". I wondered if it might be due some imbalance in the body's signalling pathways, similar to what happens with insulin in T2. Maybe, just for example, due to a bit too much or a bit too little insulin over time in T1. I googled 'malveolate pathway insulin cholesterol' as the malveolate pathway was mentioned in one of the first responses to your question.

The first one that came up was 'Updated Understanding of the Crosstalk Between Glucose/Insulin and Cholesterol Metabolism':
Glucose and cholesterol engage in almost all human physiological activities. As the primary energy substance, glucose can be assimilated and converted into diverse essential substances, including cholesterol. Cholesterol is mainly derived from de novo biosynthesis and the intestinal absorption of diets. It is evidenced that glucose/insulin promotes cholesterol biosynthesis and uptake, which have been targeted by several drugs for lipid-lowering, e.g., bempedoic acid, statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors....

The second was an intricate diagram of the pathways that, who knows, could be affected by fatty liver and diabetes (i.e. metabolic syndrome: https://www.cellsignal.com/pathways/insulin-receptor-signaling-pathway

Perhaps the answer to your question is rather complex.
 
Thanks for your research @JITR
While the link between insulin and cholesterol is interesting, as someone with Type 1 injects insulin to replace what the body would be produce if it could if it hadn't killed off all its own beta cells, I do not use any more insulin than anyone without insulin. In fact, my insulin dose is considered low.
Plus, my mother, who does not have diabetes, also experienced slowly rising cholesterol.

At the moment, I am putting it down to genetics. There are two differences due to having diabetes
- if I didn't have diabetes, I would have no reason to visit the doctor and I would have no idea what level my cholesterol was at. I am sure there is a huge portion of the population with much higher cholesterol than I have but do not know.
- there is an increased risk of heart disease with diabetes, so the threshold for statins is lower. If I did not have diabetes (but for some reason my cholesterol was tested), my cholesterol levels would not be a concern.
 
@helli,
Have you tried lowering your cholesterol with beta-glucan from oats or barley, as s'nic described in a recent post?
 
JITR said:
@helli,
Have you tried lowering your cholesterol with beta-glucan from oats or barley, as s'nic described in a recent post?
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I think you have misunderstood my question - I exercise regularly, do not smoke, my diet is low in saturated fat, high in omega-3 and fibre and I am not overweight - I am not looking to put off statins.
I asked how statins worked.
 
I take a low dose of statin (10mg) every morning. When I was on a higher dose I got regular cramp in my legs at night. I think taking statins is OK on this small dose not sure about higher unless your doctor insists!
 
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