A recent reader email asks if the skeptical cardiologist has addressed issues raised by prominent “cholesterol skeptics”:
I read with interest and appreciation your article appearing in MedPage on Omega 3s, and find myself having to inquire if you have ever addressed the cholesterol issue?
I’ve followed Uffe Ravnskov, MD, and cohorts, for years who feel it is a myth perpetuated by big pharma for enormous profits, but I have always had a major degree of skepticism coupled with a nagging uncertainty because I don’t take a statin (age 79, generally good health but with elevated levels of LDL-C, no cardiac events). My understanding is that it is of no benefit in primary prevention, questionable in secondary, no effect on overall mortality, potentially serious side effects, and might even be of benefit in older age.
So I can’t help wondering if you have ever addressed this in any of your blogs (reference please, if so) or might you going forward. Your opinion would be appreciated.
I have addressed this exact question in great detail in a post entitled “Don’t Stop Taking Your Statin Medication Based on the Latest News Headlines” but it has been a few years and I presume that it is not easily found by those like my reader who are confused by seemingly convincing scientific articles from ardent statin deniers and cholesterol skeptics like Uffe Ravnskov.
In 2019 another thoughtful reader raised the same question, this time citing a specific Rasnkov article
Nevertheless I am still confused regarding the exact role of cholesterol in the development of CAD. As a ‘layman’ who is very interested in medical issues and especially in CAD and lipid disorders, I know that a preponderance of scientific research (THE GLAGOV, REVERSAL AND ASTEROID studies for instance) have shown that low LDL (60-40 mg/dl) decreases CVD outcomes significantly and that very low LDL levels (< 60) could generate stabilisation and even regression in coronary plaque burden. On the other hand I am also aware that there are researchers who categorically deny the impact of (high) cholesterol and LDL in the development of CAD, for instance this article (with 107 references!).
https://doi.org/10.1080/17512433.2018.1519391 (LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature in ‘Expert review of clinical pharmacology’, Oct. 2018, Uffe Ravnskov et al.)
The conclusion of the article is: The idea that high cholesterol levels in the blood are the main cause of CVD is impossible because people with low levels become just as atherosclerotic as people with high levels and their risk of suffering from CVD is the same or higher. The cholesterol hypothesis has been kept alive for decades by reviewers who have used misleading statistics, excluded the results from unsuccessful trials and ignored numerous contradictory observations.
I am sure you are familiair with this paper and although I am still a firm believer in the beneficial effect of low LDL, as a ‘layman’ it is hard to comprehend why there is still so much debate regarding this issue. For the general public, as I know from discussions with friends, family members, colleagues and acquaintances, it is hard to get well informed regarding the exact role of cholesterol in cardiovascular health and disease, especially when papers contradict! At first sight the paper mentioned above gives the impression of solid research and with 107 references I must say that I am a bit impressed.
Dear Anthony: Can you, as an experienced cardiologist, clarify this contradiction? How is it these days still possible that regarding the question Does (high LDL) cholesterol causes atherosclerosis? doctor A says: yes, absolutely and doctor B says: absolutely not. ? ???
My response in 2019 was
“I totally understand your confusion. This is an area I read constantly in and have since I realized the low-fat dogma for diet was incorrect around 2013. I am a fervent believer in challenging the status quo in nutrition. I’m aware of the publications that are published challenging the LDL hypothesis. After looking at all this and approaching it from an unbiased standpoint I have to conclude that the preponderance of the evidence strongly supports the LDL hypothesis. Rather than point you at still more studies and analyses I would suggest listing to this podcast
Start at 31 minutes when Ethan Weiss, a preventive cardiologist, who I rate as truly unbiased and a free thinker summarizes the approach of Seth Kathiresan to studying the genetics of CAD. Then listen to Kathiresan summarize the different forms of evidence that support causal inference and the LDL hypothesis. It’s a nice summary of the multiple scientific lynchpins of the theory.
My first correspondent responded with two more questions:
Thank you for your reply and link. I read it and appreciated the information, very apropos to my thinking. And I really appreciated your compromise approach. I wish I heard it years ago.
It left me with a couple of questions, one general, one specific:
Does taking a statin reverse build-up? I never see that addressed.
This relates to my second question. Being 79 and no cardiac events but high total cholesterol (e.g., 275) from both high LDL C and high HDL, I’m not sure I should start, given what I read. (I seem to recall I had an ultrasound of my arteries about 10 or so years ago and nothing of major concern was noted.)
Does Taking a Statin Reverse coronary atherosclerosis?
High-intensity statin therapy has been shown by the gold-standard intravascular ultrasound technique to cause regression of atherosclerotic plaque in the coronary arteries. But as I try to emphasize (and which I just wrote about here) to patients the size of the plaque or degree of blockage of the artery is not the major problem.
Statins work on the inflammatory potential of the pimples/plaques thus lowering their tendency to progression and rupture and thereby reducing the risk of a heart attack.
The process of plaque stabilization with statin changes the composition of plaque to a more stable form with more scar tissue and calcium so scores from coronary calcium scans can go up.
Should You Start a Statin at Age >75 Years For Primary Prevention
The benefits of statin therapy are lower in primary prevention and not clearly shown in individuals over age 75. I have discussed this in detail in a post on statins in the elderly. Risks of statin side effects aren’t clearly higher in this age group but the frequent presence of comorbidities and polypharmacy increase side effect possibilities. The approach in these patients is similar to the one I outline in the post reproduced below with Geo, my father-in-law who was on the fence about taking a statin.
As an aside, an ultrasound of the carotid arteries can be read as showing “nothing of concern” but still have significant early plaque.
For the elderly patient, we are often looking at coronary calcium and vascular screening data to “derisk“. A zero CAC and normal vascular study would be a strong argument for no therapy.
Still Skeptically Yours,
N.B. The evidence that lowering LDL-C or apo B lowers risk of heart attack and stroke has only grown stronger since 2017 because, in addition to randomized controlled trials showing benefits, we now have Mendelian Randomization studies and additional drugs which lower LDL-C/apo B by mechanisms different from statins which further reduce risk of cardiovascular events.
35 thoughts on “Cholesterol Skepticism, Reversing Coronary Plaque Build-up and Starting a Statin at age 79”
My husband has been on a statin for over 20 years after having stents placed and for carotid artery narrowing. He has been doing well with very good lipid numbers. Then a few months ago he developed progressive muscle weakness. From being very strong and physically active to having difficulty standing for more than a couple of minutes without having to lean against something or sit down. He had difficulty walking very far, and was walking somewhat stooped. He was also having increasing difficulty changing from sit to stand and he developed glucose intolerance, new for him. He stopped the statin and after a few weeks the muscle weakness reversed to almost where he was prior to the onset of the weakness. The glucose intolerance is getting better but isn’t reversing as quickly. His cardiologist is leaving it up to him whether to take the statin, an alternative or nothing. His LDL is 115 at last test So while we know the statins are very beneficial for him it would be a concern to even try another type of statin. Are the non statin as effective in lowering LDL? Thank you Annie
I am caught in the same dilemma. I had a MI at age 46, a triple bypass at 48. The de rigeur treatment for me is a high-intenity statin, but I cannot tolerate statins at any dose. Typical symptoms are muscle pain and cognitive impairment. I also cannot tolerate ezetimibe as it causes gut distress. I am a medical writer with lots of experience in cardiology, but I don’t trust the data. For example, statin skeptics note that the ARR for statins is very modest (only 2.1% from pooled data from 43 major trials: https://www.ti.ubc.ca/2003/09/30/statins-benefit-for-secondary-prevention-confirmed-what-is-the-optimal-dosing-strategy).
But my cardiologist insists I take statins (rosuvastatin which is the worst!) and ezetimibe. So I must find another cardiologist who can offer viable alternatives. Any advice? Thanks. Bruce Wilson, Montreal.
You should definitely consider starting one of the PCSK9 inhibitors, either Repatha or Praluent. They are proven most efffective at lowering apo B and LDL and have no issues with muscle pain or cognitivie impairment or GI issues.
Thanks! I found a new cardio who is not so obsessed with statins, so I’ll ask him.
Maybe i missed it but I see no mention of small dense LDL particles. Recent research (based on the Women’s health init.) seems to suggest that they are the culprit in CAD. Other research suggests that statins (but maybe fibrates) are not effective in lowering the concentration of sd LDL or their ration with “good” LDL. I could give you the references but you are probably already aware of them.
on another note, the American College of Cardiology report on saturated fat reads like a novel…..what is the American Heart Association thinking.?
I have moved away from LDL particle size, particle number as a key parameter and like many authorities I believe apolipoprotein B levels give us the most reliable estimate of atherogenic dyslipidemia. This article is excellent and summarizes the area well (https://jamanetwork.com/journals/jamacardiology/article-abstract/2753612)
“Cholesterol can only enter the arterial wall within apoB particles. However, the mass of cholesterol per apoB particle is variable. Therefore, the mass of cholesterol that will be deposited within the arterial wall is determined by the number of apoB particles that are trapped within the arterial wall. The number of apoB particles that enter the arterial wall is determined primarily by the number of apoB particles within the arterial lumen. However, once within the arterial wall, smaller cholesterol-depleted apoB particles have a greater tendency to be trapped than larger cholesterol-enriched apoB particles because they bind more avidly to the glycosaminoglycans within the subintimal space of the arterial wall. Thus, a cholesterol-enriched particle would deposit more cholesterol than a cholesterol-depleted apoB particle whereas more, smaller apoB particles that enter the arterial wall will be trapped than larger apoB particles. The net result is, with the exceptions of the abnormal chylomicron remnants in type III hyperlipoproteinemia and lipoprotein (a), all apoB particles are equally atherogenic.”
so is it possible to have moderately high LDL (say 140), and low apoB lab value and therefore be at low risk for for atherosclerosis?
Yes. In discordant groups, the odds for CAC in midlife were significantly and consistently higher when apoB was greater than the median and not significantly higher than the referent when apoB was below the median, suggesting that the risk for CAC is more strongly influenced by apoB than by LDL-C and non–HDL-C in early adulthood. Therefore, this discordance analysis suggests that the measurement of apoB at age 25 years may identify subgroups (18% of sample) in which apoB levels may predict midlife coronary calcification better than LDL-C and non–HDL-C.
Howdy Everyone, Just adding my 2 cents here. I am one of those who has genetic high cholesterol. My Dad has it too. In our 20s we started having total cholesterol readings well over 300+ with LDL over 200. We were both average weight, and I could run a 5K at a 6 mile/minute pace. Anyway, my Doctor begged me to go on Statins and I resisted for a few years reading all the cholesterol skeptics out there…..
long story short – my Dad has been on Statins for 28 years now (high intensity statins) and has NEVER had a coronary event. Likewise, I started on high intensity statins in my 30s. I’m on 20 mg of Crestor and my cholesterol went from 320 with LDL of 220 down to a total of 160 with LDL around 70.
I feel great! No muscle or other problems. My Dad feels great too! Going back through our family history in the pre-Statin period (before 1970) a lot of our family members died from strokes or heart attacks in their late 40s/early 50s. That was before they tested for cholesterol!
So, no cholesterol skeptic out there (Dr. Steven Sinatra, Uffe Ravnskov, etc.) can explain why people with familial hypercholesterolemia disorders die young! If cholesterol DOES NOT matter than why have scientists and doctors proven beyond a shadow of a doubt that people like me and my Dad would die much younger without medical treatment. We are living proof of the cholesterol hypothesis!
thanks so much for sharing your family story!
What were your’s and your forebear’s eating habits? Are/were you all overweight? Eating and lifestyle habits also tend to be inherited.
My parents were obese and had cad, but I’ve lost 32 lbs weighing 153 lbs and eating a very low carb diet, mostly vegan with a little fatty fish, salads, lots of veggies, etc. Plus I eat once per day. I have controlled high blood pressure and take atenolol and amlodipine, atorvastatin, clopidogrel. No exercise chest pain, no MIs, no strokes. Exercize 6 days a week. I’m 74. No statin side effects.
Question: Can I stop the statin and clopidogrel if my lipid panel stays low?
I should add that before starting statin therapy, I was able to control LDL, total cholesterol, well with diet. My cardiologist started me on atorvastatin in Jan, 2020 because I had a EBCT coronary calcium value of 504 taken in 2011. I would love to get off the statin and clopidogrel (which my Primary Care Physician put me on in 2018 because of history of HBP and the high CAC value from 2011).
I stopped taking the statin and clopidogrel in October of last year. So, do you think I can stop the statin and clopidogrel if my lipid panel is good?
Although your diet and lifestyle are great now, you have substantial atherosclerotic plaque built up. Typically for such a high CAC score I advise long term baby aspirin and statin ( assuming no side effects) at least at a low dosage.
Thank you for the advice re: statin and baby aspirin use.
There is no simple answer to your question but I guarantee your LDL or apo B will rise significantly if you stop the atorvastatin.
Dr. Pearson, can you say anything about intermittent dosing of statins for those who are intolerant.
I have heard that it can be just as effective at driving down LDL. I would be willing to give that a shot if it means I can avoid side effects.
I’ve had great success with low dose, intermittent rosuvastatin dosing in patients who previously described problems with statins.
I wrote about this here
Edmond, I think you missed in my original post that I am in great shape, and still run 6 minute miles at 40 years old. I also am not overweight. Family High Cholesterol and eating are not related. Our brilliant scientists have linked genes that show Family High Cholesterol is a genetic disease due to lack of certain genes.
I am no scientist. All I know is I went vegetarian once and ate only vegetables for 6 months. I got my cholesterol tested after that and it was 300 with LDL of 218. Then I got my LDL particle number test and it was 2,300, which is incredibly high.
Once I got on the right statin (Crestor, 20 mg) my cholesterol dropped from total of 300 to total of 160, and my “bad” LDL dropped from 218 down to 70. All of this while I switched back to a diet including steak, cheese, eggs, etc.
By the way, I also have high Lp(A) cholesterol at 200 nmol/L. No drug can treat it, but Statins help reduce risk.
I hope this helps. I feel like so many people think they can find the magic bullet out there by eating only a certain way and avoiding “drugs”. Well, I tried and only a statin helped me.
I appreciate very much your comments. Thank goodness there’s medications that help you. I wish you the best of health.
Another good topic. A point about using statistics in drug efficacy and outcomes.
In reading there seems to be great debate about the use of use RR (relative risk) to “prop” up the performance of a drug by RX companies as opposed to looking at absolute risk. There is some validity in this observation,IMO, however I think there is a caveat, especially with statins. Specifically as Dr. Pearson mentioned, if statins were used only in high risk patients (diagnosed CVD through imaging like CAC as opposed to just LDL-C >100), I speculate that that RR % goes up and most likely it would go up a lot.
Now where I think the biggest impact is, and its not talked about enough is, exposure duration. A reasonable CVD equation would be something like this CVD mortality outcome risk= risk factors (hypertension, IR/t2d,etc) * AGE (amount of exposure to APOB) * APOB (number of atherogenic particles circulating in blood). Statins do not effect risk factors (except for reduction of HSCRP) or age but they can affect APOB dramatically which leads to lower risk, for higher risk patients. CVD is a lifetime exposure disease, meaning that the longer you are exposed to high APOB/LDL particles the higher your risk becomes. Most statins studies only look at patient outcomes for a few years and many times after an event (ischemic damage) and even then with only a year or two of lowering APOB exposure, you get something that moves the needle, which again IMO is remarkable. A great example of how APOB/LDL is causal and how important length of exposure is in mendelian randomization of people with non functioning PCSK9 (one of the major players in reducing expression of LDL-R, one of the main hepatic pathways for cholesterol disposal). They have very low lifetime APOB exposure, which in turn results in very low incidences of CVD. The longer you take a drug (PCSK9i, NPC1L1, statin) the greater benefit it will be to you because the longer you limit exposure to APOB in your vessels the less chance you have of accumulating LDL in the sub endothelial space of your arteries.
Absolute risk, I think can be misleading, in regards to CVD and APOB lowering therapies like statins because in the pool you have people that have little to no risk of CVD thrown in with people who have had MIs, strong family history of CVD or imaged CVD. The greatest takeaway is, HCPs should not rely on just LDL-C to start a statin, there needs to be better risk stratification so that the right patients get the right treatment to reduce their risk factors, not a one size fits all dogma.
Thanks for making those very useful points.
Great points as usual!
The adverse cardic events related lifeelong exposure to high apo B/LDLC is something 5 or 10 year trials underestimate.
And doctors should be using all the tools at their disposal to stratify that risk with advanced tools like apo B, lipoprotein (a), hs-CRP , CAC and vascular imaging.
I react to statins and even Zetia with allergic type symptoms. I was ready to start taking them 12 years ago since heart disease runs in my family, but the adverse reactions made me just go ahead with diet and exercise. Alas, I had a MI a year and a half ago at 57. It took a year to get on Repatha, but it is working. Too late for the MI but at least we are doing everything we can to lower LDL. Unfortunately, I just found out my Lp(a) is 300…it is discouraging. The pimples/plaque has doubled over the past year and a half. I feel like a ticking time bomb. I am glad we have new drugs but it is discouraging that it may be too late for some.
Enjoy your blog. I had a heart attack at age 40 caused by SCAD. Almost kicked the bucket! I’m now 61 and have been on statins, beta blockers and aspirin therapy ever since and am doing well. When I asked my cardiologist if I should continue on statins despite my low cholesterol numbers he said… “your are still above ground so why change!” Don’t understand folks reluctance to take stains, I have never experienced any side effects in 21 years.
It’s always good to hear stories from patients who have benefited from state of the art medical therapy. We rarely hear online from the many patients who are feeling fine and benefiting from statins by not having cardiac events (although we see large numbers in our offices) because its boring.
I would have answered differently than your cardiologist.
A common misconception is “my cholesterol #s look good therefore I can stop the statin.” Unfortunately, the #s only remain good as long as you are regularly taking the statin. They will go right back up if you stop treatment. Risk of heart attack and stroke will also go up.
Nowhere do I see the relative risk vs absolute risk controversy addressed. Ravnskov and Diamond wrote an article that showed the absolute risk between the treated and placebo branches to be @1.1% vs the frequently reported number of 36% in the ASCOT-LLA. I’m pretty sure you understand the origin of these numbers but if not you can find a complete copy of their work here: https://www.researchgate.net/publication/272189007_How_statistical_deception_created_the_appearance_that_statins_are_safe_and_effective_in_primary_and_secondary_prevention_of_cardiovascular_disease.
It is these numbers that lead to skepticism not necessarily on whether statins work but more on the nature of the true amount of good they do vs the discomforts from the side effects. The touted 36% is a big reach for what appears to be a real 1.1% difference. It’s a difficult choice for me because statins do reduce my lipid panel numbers and I do have a genetic polymorphism (rs1800206) that prevents the liver from properly metabolizing lipids. My cac increase came out to 10%/year over the last four years during which I was on and off statins at various times and for various periods of time. My hs-crp is never over .2 but it appears that also is due to the same polymorphism. It’s unclear if there is a protective impact or simply a lack of crp generation as no-one has apparently looked for a reason for this connection.
If we focus statin treatment on those who are truly high risk the benefit/risk ratio goes up. It’s also important to recognize that a high percentage of perceived statin side effects are also felt on placebo (recent study suggesting 90%).
In my experience statin side effects always go away with stopping the drug so although bothersome they are reversible.
Thanks for your reply. It’s difficult to attribute symptoms like leg cramps to anything other than the statin, especially if they come and go with stopping and restarting. Another quasi objective test is sudoku where I double or more the time on similar difficulty levels. Yes the placebo effect is something we can’t control. I’m one who can seldom distinguish differences when taking meds or supplements but these statin effects, especially the cramping, are real and repeatable.
Something else that I find interesting given the minimal differences in absolute risk is how well the placebo arm is being tested for similar levels of heart disease since it is fairly rampantly undiagnosed. To me that minimal difference might simply be at least partially evidence of those in the placebo arm having similar levels of undiagnosed disease. Are they simply using questionaires to determine disease levels or actual diagnostic procedures.
I totally agree. If legs cramps come on with a statin at a particular dosage, go away when it is stopped, and resume with another statin I consider that as evidence of statin myalgia and intolerance.
Following up on your posts about coronary calcium, LDL readings, and statin use, I have a question: I had an EBCT 10 years ago at age 64, reading 504. Since then I’ve been eating vegan, low carb with intermittent fasting. No statins. LDL and cholesterol are low (70 and 100). Q: will my dieting/fasting flush out the calcium plaques or should I get on statins asap?
Curious: How do you do vegan low carb? Vegan is mostly carbs.
Lots of olive oil, avocados, nuts, and seeds….
I eat lots of low carb vegetables, salads, Beyond Burgers, very small amounts of fatty fish, seeds, etc.
There’s quite a large group of people doing vegan keto with intermittent fasting. There are several diet books, recipe books, and online groups following this regimen. I add about 4 ounces of salmon or other fatty fish per week.