High cholesterol and statins

[Bluetit1802]

Lipid tests yeah I can see them going for that not. It's takes them all their time to do the routine ones sadly.

@Dollylolly You have had your lipids tested! You listed them in post 11

 

[Ambersilva]

Some years ago I was happily plodding along with Ezitrol controlling cholesterol levels. One day I was called in to the GP Surgery to talk about my cholesterol level of 5.8. I was told that Ezitrol does not work and that I should try statins. I was started on Simvastatin and due to unpleasant side effects other brands and strengths were tried, all with the same effects. Eventually, it was agreed that I could come off them and that I would be left alone. But that Doc retired and the replacement Doc once again revived the importance of taking statins because my level was now 7.9. I expressed reluctance for one year.

In January this year it was suggested that I try Ezitrol. But I explained to the new Doc why I was originally taken off it. I stalled again by saying that I would think about it. A test in June revealed the level was now 7.7. Reluctantly, I agreed to a trial of Ezitrol. That was started at the end of july. A blood test at the end of August astonished me. I'm back to 5.8.

Ezitrol has no unpleasant side effects - yet.

 

[DavidGrahamJones]

Ezitrol has no unpleasant side effects - yet.

Long may that continue.

 

[StevePayne]

Good morning all,

I realise that I may (will!!!) be swimming against the tide here, but I'm not against Statins....

The background for me:

I hade a medical which showed I had massively high blood pressure (170/120 - okay a bit of "white coat syndrome", but even so....) and as for cholesterol - I was pumping lard around my veins. It turned out that there is family history, no both sides. So onto BP tables and statins. BP now nicely low (still a little high) and cholesterol, nicely in the "proper" range. No side effects from the statins (started on Simvastatin, now on Atorvastatin)

Last years blood test indicated that I was Prediabetic (and, no, I'm not getting into the argument about how the goalpost move)

So, having found out some great information - a LOT on this forum (then, and still - thank you everyone!), I started on the 5:2 fasting regime and the LCHF lifestyle. Lastest info: BP just above the "normal" range (but a lot lower than it was. Cholesterol and blood sugar - right slap bang in the middle of the ideal banding. I lost 25lb, and the pain in my left knee (from carrying that weight) stopped.

My view (for what it's worth): If it works, it works

Cheers, Steve

 

[SimonCrox]

There is a lot of prejudice both negative and positive about Statins. The Daily Mail does not help; remember the Daily Mail group was pushing Brexit, but is now considering moving its HQ to Irish Republic. So the papers push all the negative effects of statins; the medical staff tend to push the positive side, and tend to underappreciate the negative side.



Is cholesterol a problem? I would agree that there are many factors influencing whether one gets a heart attack or not, but there is a clear strong correlation between higher cholesterol levels and higher heart attack rates. In trials including diabetic people, lowering the cholesterol lowered the heart attack rate; most of these trials were with statins, but have also included ezetimibe, cholestyramine and nicotinic acid. The reason that NICE recommend them is because of the proven benefit.

There is no doubt that statins are good for one’s blood vessels. And in ASCOT and HPS and other studies, this applied to diabetic people.

Remember the East and West Finland study from the early 1990’s? Diabetic Finns had the same chance of heart attack and death as non-diabetic Finns, and diabetic Finns with heart attack on average only lived a few years. This awful situation has been improved dramatically so that diabetes is not now considered “Coronary Heart Disease Equivalent”, due to addressing all the factors including cholesterol, and indeed the STENO investigators thought that cholesterol was probably the most important factor to address (of course one has to tackle all factors cos some one might not be able to alter much).

It is clear that statins raise the blood glucose, but generally this effect is unnoticeable, and given the outcomes of the above trials and others such as STENO, the generally small increase in glucose is less important on balance than the significant reduction in heart attacks.

Some people do get confused on them (and they are all the same), and some folk do get sleep disturbance.

The muscle aches are the really difficult part, because lots of people get muscle and joint pains without statins. I would also point out that several trials, particularly HPS, had a run in with everyone taking a statin, and if side effects developed, then the subject was excluded from the trial, ie the trial selected subjects who were less likely to get side effects.

A different way to think about it is to consider what happens if one’s plan goes wrong. If one takes the stain and gets side effects, one is watching for the side effects, spots them early and no long term harm done; if one has a heart attack later, at least one can say that at least tried statin. If one does not try the statin, and one has a heart attack, one cannot replace the dead heart muscle.

Are there other options? Ezetimibe was shown to be beneficial in the IMPROVE-IT trial; indeed looking at the figures, is probably only beneficial in diabetic people, and is probably not quite as good as a statin. It is however much better tolerated with only about 1 in 1000 getting side effects vs about 1 in 20 with statins (which means that 19 out of 20 are OK). If one wishes, one can try a small dose of a statin alternate nights to help the ezetimibe. Nicotinic acid and cholestyramine are generally so unpleasant to take that no one takes them. It is early days for PCSK-9 inhibitors.

I would also point out, that if not “To Target” on a statin, doubling the dose decreses cholesterol only 7%, so better to switch to a “stronger statin” if possible, or add in ezetimibe.

I hope that I have provided a balanced view of the topic.


Ezetimibe was shown to work and have few side effects with publication in 2015; http://www.nejm.org/doi/full/10.1056/NEJMoa1410489

 

[Guzzler]

There is a lot of prejudice both negative and positive about Statins. The Daily Mail does not help; remember the Daily Mail group was pushing Brexit, but is now considering moving its HQ to Irish Republic. So the papers push all the negative effects of statins; the medical staff tend to push the positive side, and tend to underappreciate the negative side.



Is cholesterol a problem? I would agree that there are many factors influencing whether one gets a heart attack or not, but there is a clear strong correlation between higher cholesterol levels and higher heart attack rates. In trials including diabetic people, lowering the cholesterol lowered the heart attack rate; most of these trials were with statins, but have also included ezetimibe, cholestyramine and nicotinic acid. The reason that NICE recommend them is because of the proven benefit.

There is no doubt that statins are good for one’s blood vessels. And in ASCOT and HPS and other studies, this applied to diabetic people.

Remember the East and West Finland study from the early 1990’s? Diabetic Finns had the same chance of heart attack and death as non-diabetic Finns, and diabetic Finns with heart attack on average only lived a few years. This awful situation has been improved dramatically so that diabetes is not now considered “Coronary Heart Disease Equivalent”, due to addressing all the factors including cholesterol, and indeed the STENO investigators thought that cholesterol was probably the most important factor to address (of course one has to tackle all factors cos some one might not be able to alter much).

It is clear that statins raise the blood glucose, but generally this effect is unnoticeable, and given the outcomes of the above trials and others such as STENO, the generally small increase in glucose is less important on balance than the significant reduction in heart attacks.

Some people do get confused on them (and they are all the same), and some folk do get sleep disturbance.

The muscle aches are the really difficult part, because lots of people get muscle and joint pains without statins. I would also point out that several trials, particularly HPS, had a run in with everyone taking a statin, and if side effects developed, then the subject was excluded from the trial, ie the trial selected subjects who were less likely to get side effects.

A different way to think about it is to consider what happens if one’s plan goes wrong. If one takes the stain and gets side effects, one is watching for the side effects, spots them early and no long term harm done; if one has a heart attack later, at least one can say that at least tried statin. If one does not try the statin, and one has a heart attack, one cannot replace the dead heart muscle.

Are there other options? Ezetimibe was shown to be beneficial in the IMPROVE-IT trial; indeed looking at the figures, is probably only beneficial in diabetic people, and is probably not quite as good as a statin. It is however much better tolerated with only about 1 in 1000 getting side effects vs about 1 in 20 with statins (which means that 19 out of 20 are OK). If one wishes, one can try a small dose of a statin alternate nights to help the ezetimibe. Nicotinic acid and cholestyramine are generally so unpleasant to take that no one takes them. It is early days for PCSK-9 inhibitors.

I would also point out, that if not “To Target” on a statin, doubling the dose decreses cholesterol only 7%, so better to switch to a “stronger statin” if possible, or add in ezetimibe.

I hope that I have provided a balanced view of the topic.


Ezetimibe was shown to work and have few side effects with publication in 2015; http://www.nejm.org/doi/full/10.1056/NEJMoa1410489

People with 'normal' levels and even low levels have heart attacks. As far as I am aware causal proof that high cholesterol is a predictor of CVD/CHD has not been shown.

 

[DavidGrahamJones]

I realise that I may (will!!!) be swimming against the tide here, but I'm not against Statins....

Not at all, everyone accepts that we are all affected differently some good and some bad. You'll probably find that that those who had problems (mine were severe leg muscle pain, poor sleep and brain fog) aren't necessarily against statins but more against the idea that they're wonderful for everyone. As if our problems were imaginary. This is in fact made worse by the powers that be "hiding" the results from clinical trials, although Merck Pharmaceutical's patent application in 1990 made it perfectly clear that from their clinical trials there were problems caused by statins preventing the uptake of CoQ10.

Like you, I'd say "if it works . . . . ". Now, how do you know how low you want your cholesterol. Something decided in the US (initially) by a panel of 9 judges, 8 out of whom were paid by the pharmaceutical companies. A bit like the litigant in a court case being related in some way to the judge.

 

[Tabbyjoolz]

I had my diabetic review yesterday with my favourite doctor at my practice. TBH, I had done the blood tests in July and had put off making the appointment for the review because the senior doctor at the practice had taken exception to my total cholesterol rise and had not only arranged for a statins prescription but DID NOT CANCEL THE PRESCRIPTION when I complained.

Favourite Doctor noticed my HDL had risen considerably and that my LDL had fallen - again - and sympathised about the statin mess as he could see on my notes that I have consistently refused them. He was quite excited about my LCHF diet as my Hba1C had held steady and that my LDL is falling.

Later I ran the figures through HughCalc and apart from a "borderline" for my total cholesterol score, I scored Optimal and Near Optimal for the other figures.

 

[DavidGrahamJones]

there is a clear strong correlation between higher cholesterol levels and higher heart attack rates.

I trust the World Health Organisation. I'm looking for that clear strong correlation. Admittedly they are death rates rather than events.

I could be wrong, but all deaths and cholesterol levels looks as confusing as CVD deaths against cholesterol levels.

The WHO with the British Heart Foundation produced the chart which is in a PDF and say that there is a correlation between total cholesterol and cardiovascular disease and it's very weak.

 

[SimonCrox]

I trust the World Health Organisation. I'm looking for that clear strong correlation. Admittedly they are death rates rather than events.
View attachment 23840
View attachment 23841

I could be wrong, but all deaths and cholesterol levels looks as confusing as CVD deaths against cholesterol levels.
View attachment 23842
View attachment 23843

The WHO with the British Heart Foundation produced the chart which is in a PDF and say that there is a correlation between total cholesterol and cardiovascular disease and it's very weak.

There is a lot of truth in what you say; there are many risk factors for coronary heart disease (CHD), and on its own, cholesterol is a weak predictor. In folk with no other problems ("Primary Prevention"), WOSCOPS showed that a statin prevented CHD events, but it was not dramatic, and the benefit was greatest in men with non-specific chest pain or ECG changes (I think ) ie they probably had established CHD, particularly coming from the Glasgow area.

The international data that you show is really interesting, and it demonstrates the risk, as you say, of observational data. So, on the pdf link, there is a lower mortality with lower cholesterol, but these are countries like Kenya where they are probably dying of something else infectious and this is lowering the cholesterol.

Looking at mortality is quite a good trick; firstly it is generally an easy diagnosis to make, and secondly, there is no point in taking a treatment to avoid a heart attack if you rapidly drop dead from something else.

But I think that one needs to focus on a western population with western lifestyles and disease. When the Japanese moved from Japan to USA after WW2, within one or two generations, the low CHD risk of native Japan had risen to match the high risk on native USA. The statin trials can be lumped together to look at the event rate by cholesterol level and one gets the same sort of graph as your WHO charts, except the line has completely the reverse slope! But I would rush to point out that these are trials in high risk populations who have either had a coronary event or have lots of coronary risk factors.

To show causality of this link is difficult, because one is never sure in observational studies what causes what. Does high / low choleterol cause something? Does an illness alter the cholesterol? Does another factor alter both cholesterol level and health? And it is likley that what happens differs in different populations.

So, I can attach the chart showing fewer CHD events with lower choleterol, and MRFIT showing that different factors are additive. But the original question is whether statins help, by whatever mechanism, but probably cholesterol reduction? So many studies (in folk at high cardiac risk) showed the benefit of statin therapy. Pravastatin is a weak statin, and the makers were trying to say it is some other effect of statin, not particularly cholesterol reduction, that does the trick; so in PROVE-IT, folk at risk got either average dose paravastatin or decent dose atorvostatin; the decent dose atorvastatin dropped the cholesterol more and prevented more cardiac events.

I guess at the end of the day, in a person with a low number of coronary risk factors, the cholesterol is not very predictive and treating does not make much difference, but in a higher risk population, the cholesterol is a better marker of risk and treatment is more benficial. So, it is a case of seeing what trial subjects matched oneself, and what the treatment did to them.

 

[Guzzler]

But it is this "lumping together" of data to come up with these observational studies that can and does skew the so called findings without RCTs that has led to half the planet being put on statins. I think that in older people without a history of cardiac events to be put on statins with even the minimal benefit of lowering cholesterol when the 'data' does not show that cholesterol is causal is nothing short of a scam.
Statins bring in the most $$ to big pharma and yet there is no definitive evidence to support the use of said.
As for how they came up with the recommended healthy level of cholesterol is beyond me.

 

[SimonCrox]

But it is this "lumping together" of data to come up with these observational studies that can and does skew the so called findings without RCTs that has led to half the planet being put on statins. I think that in older people without a history of cardiac events to be put on statins with even the minimal benefit of lowering cholesterol when the 'data' does not show that cholesterol is causal is nothing short of a scam.
Statins bring in the most $$ to big pharma and yet there is no definitive evidence to support the use of said.
As for how they came up with the recommended healthy level of cholesterol is beyond me.

PROSPER looked at folk aged 70 to 82, and HPS looked at folk 75 to 80; they all had other vascular risk factors such as hypertension or diabetes or established vascular disease. Both studies showed benefit; and both took folk with choletserols above 4.0 mmol/L. So, I would agree that putting all the elderly on statins blindly is inappropriate, but ageing is a strong risk factor for coronary events and if there were other risk factors, then considering a statin is OK. But having started, one would need to know when to stop eg if developed a terminal cancer or going into nursing home care.

As to the target level, I quite agree; most studies just gave the statin and did not have a target. I am not really sure how the target was decided.

Most of the statins are generic now and cheap; the UK spends less now on statins than 10 years ago despite treating more people. I would never condone deceitful practice by anyone, including pharmaceutical companies, and one needs to look at any evidence oneself, not accept in spoon fed fashion the info from pharma; but if there were no pharma companies, there would be very few drugs. Such is life

 

[Guzzler]

PROSPER looked at folk aged 70 to 82, and HPS looked at folk 75 to 80; they all had other vascular risk factors such as hypertension or diabetes or established vascular disease. Both studies showed benefit; and both took folk with choletserols above 4.0 mmol/L. So, I would agree that putting all the elderly on statins blindly is inappropriate, but ageing is a strong risk factor for coronary events and if there were other risk factors, then considering a statin is OK. But having started, one would need to know when to stop eg if developed a terminal cancer or going into nursing home care.

As to the target level, I quite agree; most studies just gave the statin and did not have a target. I am not really sure how the target was decided.

Most of the statins are generic now and cheap; the UK spends less now on statins than 10 years ago despite treating more people. I would never condone deceitful practice by anyone, including pharmaceutical companies, and one needs to look at any evidence oneself, not accept in spoon fed fashion the info from pharma; but if there were no pharma companies, there would be very few drugs. Such is life

People over seventy have a greater risk of death, period. Other than that, I agree with you.

 

[SimonCrox]

People over seventy have a greater risk of death, period. Other than that, I agree with you.

yes; one should add life to years, not years to life!

 

[Guzzler]

yes; one should add life to years, not years to life!

Agreed. Years added in pain is means a lower quality of life.

 

[DavidGrahamJones]

I am not really sure how the target was decided.

An interesting read. I believe the UK is heavily influenced by the US.

http://www.nature.com/news/cholesterol-limits-lose-their-lustre-1.12509

 

[SimonCrox]

An interesting read. I believe the UK is heavily influenced by the US.

http://www.nature.com/news/cholesterol-limits-lose-their-lustre-1.12509

Interesting article.

I think the Americans aimed to get cholesterol levels lower than UK doctors, but agree we have been dropping target level for years. Blood pressure is another example of the targe reducing, until 2015 (I think) when it was relaxed to 140 systolic.

The article is also salutatory regarding the guy's treatment - pushing the statin dose caused side effects; if one doubles any statin from 40 to 80 mg, the cholesterol level drops a bit (eg 7%), but the risk of side effects goes up a lot (eg from 3% to 8% with atorvastatin). Adding ezetimibe would get more reduction for the lower level of side effects. One needs a clinician who understands the illness and treatments.

“We can’t just assume that modifying the risk factor is modifying risk,” says Harlan Krumholz, a cardiologist at Yale University in New Haven, Connecticut. “We’ve been burned so many times in the past decade by that assumption.”. This statement is true, but there is so much evidence that modifying risk factors eg cholesterol, high blood pressure (BP) and smoking is beneficial. The clofibrate experience showed us that dropping the cholesterol decreased heart attacks, but increased mortality due to gallstones - we noted this in the 1970's.


Krumholz’s scepticism is rooted in experience. In 2008 and 2010, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial challenged dogma when it reported that lowering blood pressure or blood sugar to prespecified targets did not reduce the risk of heart attack or stroke. In the case of blood sugar, the risks were worsened. The trial demonstrated the folly of assuming that risk factors must have a causal role in disease, says Robert Vogel, a cardiologist at the University of Colorado, Denver. “Short people have a higher risk of heart disease,” he says. “But wearing high heels does not lower your risk.”

This is not the whole story; ACCORD did show that reducing the blood pressure to 120 systolic I think, did decrease the stroke rate, but increased the side effect rate, so it was deemed inappropriate to aim for 120 systolic; ADVANCE had similar findings. ACCORD found the a low HbA1c target was not particularly beneficial, but they dropped the HbA1c to low levels over just a few months. In ADVANCE, similar HbA1c targets were set, and wer more beneficial because of fewer side effects because HbA1c was reduced over one year,

I totally concur with the sentiments of the article that aggressively chasing targets is not always helpful. Firstly, if someone has a sky high HbA1c or BP, the first decrease is much more beneficial than the last decrease. So, if nearly to target, and risk of side effects from drugs, I would leave alone. There is a story of an 85 year old referred for insulin therapy cos her HbA1c was 0.2 % above the target of the time! Secondly, STENO showed dramatic benefit, in a Target driven study, but actually, very few folk reached all 3 targets; this was a group with microalbuminuria who would do badly without treatment.

All NICE guidance starts with a apragraph along the lines of an informed clinician discusses the problem with the patient and together they do what they feel is appropriate, a guideline is just a guideline. But very few folk read this bit!