I need to keep reminding myself and the people I take care of... it's often very hard to build these structural changes into our busy, stressful lifestyles that are by default exhausting and sorely in need of simple pleasures! I get it.
And many of us do. I have found that the maybe 5 minutes my PCP spent with me advances my skepticism concerning the “care” they simply do not seem to have time for. More like going through a car wash. Would I be trusting a casual comment about starting a statin? No!
Very true, don't hate the players, hate the game, right?
I do think that consulting with experts in any field - plumbing, investing, doctoring - involves some respect of their implicit experience and knowledge, and they should be allowed and indeed expected to offer advice and fixes without fully educating us about the nuts and bolts... but as you can see from the "horribly complicated but great review article" linked in the beginning - the nuances are just so paralyzing that we are often forced to oversimplify and offer blanket recommendations. It's such a tough job being an informed patient or an informed doctor!
Excellent! And yes all doctors love for their patients to quote any journal. 🙄 But we do have to be more collaborative while trying to educate and I’m down for that. I’m in the group that is low risk for heart disease so far and I do all the lifestyle things. But my cholesterol is creeping up. I’m resisting taking a statin and my PCP isn’t pushing yet.
Agreed, and you know the risks/benefits/highs/lows of self-education. It can be great for patients, and generally I encourage it as part of that collaboration you're talking about. But for patients and providers alike, the bottom line consensus guidelines that experts labor over are essential for primary care docs especially, as we shouldn't be expected to be masters of every study out there. Synthesis is a gift!
I run the AHA calculator all the time to determine if someone needs a statin, and with their flat dose response curve, I always start low. My PCP has told me that most of her patients “age into a statin “— she has a mostly female panel. Women over 50 tend to creep up with their lipids, even with healthy habits.., thanks as always, for the deep dive and thoughtful discussion.
Agreed. Many of my female patients increased LDL after menopause. Not sure if it was age or changing hormones. Many proved responsive to small doses of statins like 5 mg of rosuvastatin twice a week.
Same experience here. And the American College of Cardiology did put out this statement back in 2013... a bit dated but I couldn't find anything more authoritative and recent upon a quick search:
The following are 10 points to remember about alternate-day dosing with statins:
1. There is evidence favoring primary prevention with statins for high-risk patients. Patients with coronary disease should be treated with statins to achieve an low-density lipoprotein cholesterol (LDL-C) <100 mg/dl and <70 mg/dl for very high-risk patients.
2. While the decrease in mg/dl per mg of statin varies, the linear incremental dose response is similar with each of the statins. The percentage of patients who obtain the target LDL-C level of <100 mg/dl is 70% with 10 mg of atorvastatin, 82% with 20 mg of atorvastatin, and 89% with 40 mg of atorvastatin.
3. The efficacy of intermittent dosing of statins relates to the fact that the duration of the cholesterol-lowering effect of the statins is not related to the pharmacokinetics of the individual drug.
4. Steady-state statin drug levels may be achieved in a few days, but steady-state LDL-C reductions take several weeks to achieve, and after discontinuation, it takes several weeks before the cholesterol level returns to baseline.
5. The cholesterol-lowering action of alternate-day statins is as effective as daily dosing in many individuals.
6. To maintain the same degree of decrease in LDL-C when giving the statins on alternate days, the dose of the statins frequently needs to be increased.
7. Alternate-day statin administration seems to decrease the incidence of its adverse effects, particularly myopathy.
8. The effect of alternate-day statins on its many pleiotropic effects is unknown; thus, the efficacy for reducing cardiovascular events is not established. In small cohorts of patients, atorvastatin 20 mg daily decreases the high-sensitivity C-reactive protein (hs-CRP) by 35% compared to 22% with 20 mg atorvastatin every other day (p = 0.08), and there is no difference when baseline hs-CRP is <1 mg/dl.
9. Alternate-day dosing of statins provides cost savings.
10. Large-scale studies with outcome endpoints and prolonged follow-up are needed to substantiate the hypothesis that alternate-day statins are an equivalent strategy for reducing cardiovascular events.
I do the same - we have a drop down, built in 10 year risk calculator in Epic that does provide a quick point of care discussion point... but like you said post-menopausally we really see the cholesterol numbers climb in women, despite no major changes in diet/lifestyle. I'm guessing this and a host of other estrogenic effects that fade away explain how women's CV risk catches up to men in about 10 years after menopause. Thanks for stopping by, Jan :)
When my father was taken off of statins, he improved within days. Aches diminished. Strength increased. So the question from this anecdote is: How can one figure out that a specific person isn't well-suited for statins therapy?
Yes, but...
Are there any data about blood lipid levels being affected by getting Covid? Whether you answer or not, that's something I'll be asking my own PCP in a few months. Sometimes asking a question with no clear answer, or getting an answer you don't expect, is quite useful.
Hi Jerry - Yes, but... I agree there is never a one-size-fits-all answer or experience with medicines. If someone stops a statin, feels better, then restarts it and feels worse, then stops it again and feels better - you really have to take them at their word! Of course this is not a blinded experiment, but asking a person to set up their own double-blinded placebo controlled self testing is just not reasonable :)
And the answer with Covid seems to be always, "Yes, and..."
You name it and Covid can mess it up, including cholesterol metabolism:
Great summary of the issue. I'm a big statin advocate but always inform patients up front of this increased risk of DM (and myalgias). it's important also discuss the nocebo effect and the widespread misinformation about statins on the inter web during the opening statin conversation.
The DM risk has been troubling me for the last 5 years and with this latest meta-analysis (of good RCTs) it has accelerated my tendency to offer adding ezetimibe to 10 mg rosuvastatin versus bumping rosuvastatin to high-intensity levels (20-40mg) when seeking additional LDL/apo B lowering.
These approaches have similar LDL lowering power but less myalgias and DM risk with the combo.
I was hoping you would stop by, and I'm relieved that you find this a great summary, phew!
Your strategy here makes great sense. I think it dovetails with the ACC guidance on this in general, although I know as an individual practitioner you are in the zeitgeist:
I don't use a lot of Zetia because the outcomes data remains kind of weak, right? But makes sense as an add on or alternative with the statin side effects, dose dependent risks, etc. Thanks again!
I also appreciate this! Great to have an evidence-based and helpful medical professional community here on Substack... there is a lot of the opposite here, too. I'm building a network of trusted sources.
Thanks for this great nuanced review, Ryan! My doctor has suggested statins for me based on my high LDL-cholesterol. I have batted that away since I’m young, do high intensity exercise and strength training 3-4 days a week, and don’t smoke. However, I’m reading “Outlive” by Peter Attia now and he makes similar points about the cumulative longterm effects of high cholesterol and the importance of preventing plaques looooong before there are signs of heart disease. On the other hand, diabetes runs on my mom’s side and my fasting BG chronically runs a few points high (although my A1C is chronically LOW, and I have not been able to reconcile those discrepancy facts!)
What do studies show about the impact of statins on *all cause mortality* for patients with and without diabetes? That data would seem to get around whether or not the marginal added risk of hyperglycemia makes a significant difference
Hi Eric! Thanks for the case study here, and I am also slowly working my way through "Outlive". Very slowly! In general he is way aggressive, and makes some conjectures and best guesses... but they do sound intuitive in terms of looking at a 20, 30, 40 year time horizon. Nothing replaces diet, exercise, etc but the argument for statins over the long term before cardiovascular disease is present makes intuitive sense. Wish there were more studies to prove this. Some people hedge their bets with low dose rosuvastatin most days of the week, maybe alternate day dosing for example. But with diabetes the outcomes data definitely favors starting a statin, such that it is really standard of care. More information than you need but I'll copy and paste from UpToDate:
Lipid management — Lipid abnormalities are common in patients with diabetes mellitus and undoubtedly contribute to the increase in risk of ASCVD. The ADA recommends screening for lipid disorders at the time of diabetes diagnosis, at an initial medical evaluation, and every five years thereafter if under age 40 and annually if indicated, as is usually the case in patients age 40 and older [20].
We and others recommend lifestyle intervention (diet, weight loss, increased physical activity) to improve the lipid profile in all patients with diabetes [20,66].
●Primary prevention – The ADA recommends the initiation of at least moderate-intensity statin treatment for all adults with diabetes between the ages of 40 and 75 years [20]. For patients without additional ASCVD risk factors and a baseline LDL cholesterol close to target, we individualize the decision to initiate statin therapy. This decision can be informed by use of an ASCVD risk calculator. (See "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults: Our approach", section on 'Estimate ASCVD risk using a risk calculator'.)
For individuals aged 40 to 75 years with diabetes and at least one additional cardiovascular disease risk factor, the ADA recommends high-intensity statin therapy with treatment targets of an LDL cholesterol <70 mg/dL (1.8 mmol/L) and a reduction from baseline LDL cholesterol level of at least 50 percent. For individuals with diabetes aged 20 to 39 years or >75 years, the decision to initiate statin therapy should be individualized. For adults with diabetes aged >75 years in whom statin therapy was initiated previously, treatment continuation is reasonable. Approaches to lipid-lowering therapy in individuals with diabetes may vary, and ADA recommendations differ from those of other society guidelines. (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease", section on 'Diabetes'.)
●Secondary prevention – In patients with clinical ASCVD, high-intensity statin therapy should be added to lifestyle intervention regardless of baseline lipid levels. The ADA treatment targets include an LDL cholesterol <55 mg/dL (1.4 mmol/L) and a reduction from baseline LDL cholesterol level of at least 50 percent [20].
Thanks for the detailed info, Ryan! That all makes a ton of sense. I am still trying to wrap my head around fasting hyperglycemia with low A1c (maybe poor sleep? stress?) but according to the ASCVD calculator you provided my risk is quite low and a statin wouldn't be recommended by current guidelines. I can chat more with my pMD at my upcoming annual physical this summer 👍
I agree with your basic take on Outlive, and I will be publishing a book review on it in a week or so. He is definitely aggressive and suggests things that I doubt insurance would cover, although some of those recommendations that would have been considered "aggressive" when the book was written a couple years ago are already becoming mainstream, like pushing colon cancer screening earlier than 45. I am overall impressed by his rigor of analysis of the literature, and unlike many quacks out there he constantly talks about EBM concepts, NNT, absolute vs risk reduction, trade-offs, uncertainty, etc. He is also refreshingly frank about the limitations of EBM and doesn't fall into the trap of pedantry like VP and the SM crowd, screeching "BuT ThErE's No RCT FoR ThiS!!" even when it is a low-risk intervention for which that type of study could not be easily or ethically done. He also walks a fine line of being neither a shady product/supplement hawker nor going full "alternative medicine" and bashing pharmaceutical interventions.
Whether some of his approaches are borne out by longitudinal studies remains to be seen, but I think his work through his book, podcast, and other activities are making a huge beneficial contribution in three ways: (1) focusing on prevention rather than reactivity, (2) trying to improve QUALITY of life as much as or more than QUANTITY (I actually think "Outlive" is a bit of a misnomer for his actual views), and (3) placing the biggest emphasis on lifestyle interventions medicine has largely neglected until recently, like diet, exercise, SLEEP!, and emotional health / stress management.
Such a good review, and I will look forward to reading your actual post... although you could save yourself some time and just cut-and-paste this excellent comment!
I need to find the time to read the rest of his book, but that pesky sleep notion keeps creeping in. I'm struggling to hit those 7 hours, but mostly getting at least 6 which is not great.
I'm reading the diary of Ann frank right now in preparation for a trip to Amsterdam this summer. I saw one of your notes that you might have just been there? I'll try to catch up on everything tonight/this weekend... and read more Attia on the plane soon. He also comes across a bit arrogant, speaking as a former surgeon who claims to have been disillusioned by the reactive practice of medicine, and like he's the only guy in the room who thinks of reframing medicine 3.0 around prevention... maybe he could have taken a severe pay cut and joined me in the trenches of primary care, where most of us primary docs happily serve and do counsel about prevention ALL THE TIME!
Sorry I also meant to give this a sincere ❤️ and 👍
“ He is also refreshingly frank about the limitations of EBM and doesn't fall into the trap of pedantry like VP and the SM crowd, screeching "BuT ThErE's No RCT FoR ThiS!!"
Interesting you write about this today, as yesterday I had a long overdue lunch with two friends, a retired nurse and a truly extraordinary NYU prof of PT who has helped both my nurse friend and me enormously. The question as to whether and when to take statins came up. They both observed that, despite excellent exercise and nutrition regimes, which they both have—I’m decent, but not by any means in their league—it seems inevitable that, as you age, LDL goes up, and then the question is what to do about treatment and when. They both agreed existence of more than minimal level plaque was an important criterion (about which I learned first from you and from commenters on one of your earlier posts). The PT Prof also continues to find the ratio of HDL to overall cholesterol, 3.5:1 being optimum, if I remember rightly, a useful indicator. I am curious about any thoughts you might have on the whole set of possible indicators, and particularly the ratio, as I don’t see that referred to as much these days.
Hi Susan - very good points, and the nuances regarding statins will continue to be teased out, debated, and weighted for many years. But on the whole, for people with higher risk problems and lifestyles, the benefit seems clear, and the overall risks low. Family history is kind of an X factor that doesn't make it into a lot of the calculators, as they pull from studies like the Framingham study that did not have reliable family history data to mine (my understanding). The addition of the coronary artery calcium scan (CAC), usually paid for out of pocket for maybe $150, can add some real evidence for who is actually laying down plaque and therefore a great candidate for statins. The Skeptical Cardiologist (commented above) has some excellent articles on this!
Oh, yes, it was the Skeprical Cardiologist I was thinking of. He has really useful information—although sometimes over my pay grade, I learned a lot from hi, as I do from you!
"Kind of. Not really. Sort of." That's unfortunately all the time (and perhaps knowledge) many primary doctors have to break this stuff down. Appreciate the expanded conversation here!
I would also add that HBA1c stands for "hemoglobin A1c" and is used to estimate average blood sugars over the past 2-3 months, right? What are the normal/diabetes ranges? Above 6.5 is type 2 diabetes still?
Hi Grant - and I'm sure I'm guilty of this kind of short hand when running 40 minutes late and tending to some patients with problem lists into the 30's! But I try when I can to expand the dialogue and meet people where they are... this post might have been built upon too may assumptions, like HBA1c being a familiar concept. But you got it - <5.7 or so is normal, 5.7 - 6.5 is pre diabetes or impaired fasting glucose, and >6.5 is the agreed upon definition of diabetes. There is a continuum of risk that goes up with the HBA1c, but the 6.5 number is the inflection point where significant complications like diabetic retinopathy really start to develop over time. Kind of. Sort of ;)
5 years ago, at age 63, my total cholesterol bumped just above normal on yearly labs, triglycerides & HDL normal. My doctor put me on Rovustatin, telling me, "you have a great risk of having a heart attack or stroke within the next 10 years, without it". After a couple of months my legs began to feel like they were going to sleep, so I went back to her. No other statin was suggested. She was my doc of 8 yrs. & once told me that "I am the Dr. & you are the patient" & to just take the statin, which felt pretty crappy at the time for this older nurse. I had questioned her about how people could take a statin & feel this way. So I stopped it & didn't see her again before I retired & we moved to the NW.
New PCP here noted that my LDL went up "quite a bit" , which was higher after quitting the Rovustatin for a year. He hadn't seen the years of normal cholesterols. He started me on Atorvastatin, which I tolerated for about a year & then, last month, my new PCP, a DO recently out of school, tells me on the 1st visit that, "the statin will not benefit you". I had just started having the leg pain, now also with a rash on lower legs. Both gone after 2 days when I quit taking statin after that visit. I see him again in 6 months. Glucoses had been creeping up & had been normal before statin.
I'm 68 now, retired 3 years ago from a long 45 year ER nurse career.
Now, work with a trainer & work out 4 days/week. I eat now & have to work to get 1800 cal a day in... increased water intake, starting in the morning. I'm also now able to sleep, go to yoga class. I feel great, take very few medications after living on Advil for years. Joined the Garden club & Soroptimists. BP rarely up, almost zero migraines after 10 a month for years. The CAC is a test that I would pay for, but what then?
I'm grateful just to have a PCP, as we seem to be in a bit of a medical desert here for boomers, with providers coming & going while employed by 1 of 2 hospital systems in the valley.
I'm always open to less medications & doing what I can to improve my chances of being around a number of more years to enjoy the grandkids & life.
Hi Nurjam - and thanks for this comment, it is really instructive. This one had me cringing!
"I am the Dr. & you are the patient"
Eww!
There is a definite psychology to taking medicines, and with statins in particular we tend to back off the healthy behaviors thinking the medicine has us covered... but like you said there is no substitute for the hard work of eating well, exercising, and all the rest... which end up making us feel much better anyway! Unless we are like the millions of folks with long Covid post-exertional malaise or other medical problems wherein exercise is not great/possible. I'll keep exercising and eating fairly well with you as long as I can, and I'm glad you have a PCP. The field has been decimated and neglected lately, with up to 30% of docs leaving since the pandemic I think, and a big shortage of residents in training. Thanks for stopping in :)
Thank you Ryan, This info was timely for me. I was recently started on a statin. My Hb A1c was borderline for pre diabetes and both my parents had diabetes. A CT done for a different reason did show some atherosclerosis of my abdominal aorta ( not surprising at age 72). So despite a low BP and no personal cardiac issues a statin seems a good choice. I will continue diet and exercise efforts. Marty
Thanks Marty for sharing, and I think your choice is a good one, with lots of evidence that statins help reduce risk when atherosclerosis is detected regardless of our obsession with LDL. I know you'll keep up with the diet, exercise, stress reduction, and California state of mind which all combine to be more important than the statin. Let's hope for a calm November, and better times ahead for the world. Let's chat soon and I'll share what "we" are doing re: statins lately, too ;)
I do like patients to advocate for themselves but too many are not equip to understand the nuts and bolts of studies. Instead they rely on MSM and anecdotal 'information'. This is a nice article. https://www.medicalnewstoday.com/articles/safest-statins#summary
Bottom line, no therapeutics without risks. Maybe a printout would help.
So true, KB, thanks for adding this. Actually one of my patients ( a reader) told me today that a lot of my articles have become a bit complex for her lately. So hard to strike a balance between writing about stuff on a different level than people can get from your average "medical/health newsletter" and getting too wonky. I'll have to throw in some more quick ones soon for her at least :) And yes, nothing without risks - always weigh risks, benefits, alternatives.
Thanks again for a great column. I think it's really important to stress that for secondary prevention, there really isn't a question about benefit outweighing harm. When I was a resident in the hospital I trained at, which is the largest hospital in the state and the main stroke centre, I managed I managed to get lipid profile taken off the "routine" bloods done post ischaemic stroke by pointing out the futility of doing them soon after a stroke, and also that it wouldn't change management. Mind you, this was in the days before PROVE-IT and PCSK9 inhibitors! I also recall having arguments with the cardiac nurse for refusing to order lipid profile in ACS patients for the same reason. They complained to the attending who happily agreed with my reasoning.
When it comes to primary prevention, the rationale can be far more nuanced, but I often have little time to delve into the nuances since they're usually not there to see me for that! If only we had more primary care doctors like you Ryan!
For what it's worth, my usual go-to is pravastatin since I have the impression it actually led to improved glycaemic control in the trials, and I think I've seen some advertising/opinion that pravastatin also isn't bad for glycaemia, though it is not widely used at all in Australia. There have been observational studies suggesting that lipophilic statins might lead to worse outcomes in PD, so I often such l switch my PD patients to hydrophilic ones, and there is also a risk of reversible cognitive impairment with the lipophilic ones, so worth keeping in mind if you have a patient with cognitive issues on a statin.
Very insightful and helpful comment, thank you! Totally agree with primary versus secondary, and questioning whether a test will change the plan is important. Agree with lipophilic statin preference, and need to give pravastatin more respect. We are pretty into rosuvastatin here…
perfect close: "never rely on medications over lifestyle improvements like exercise, weight loss, and a heart healthy diet"
Agree. Unfortunately, some patients don't embrace the changes.
I need to keep reminding myself and the people I take care of... it's often very hard to build these structural changes into our busy, stressful lifestyles that are by default exhausting and sorely in need of simple pleasures! I get it.
You know, that conclusion seems to be a common thread on almost everything, doesn't it??
And many of us do. I have found that the maybe 5 minutes my PCP spent with me advances my skepticism concerning the “care” they simply do not seem to have time for. More like going through a car wash. Would I be trusting a casual comment about starting a statin? No!
Very true, don't hate the players, hate the game, right?
I do think that consulting with experts in any field - plumbing, investing, doctoring - involves some respect of their implicit experience and knowledge, and they should be allowed and indeed expected to offer advice and fixes without fully educating us about the nuts and bolts... but as you can see from the "horribly complicated but great review article" linked in the beginning - the nuances are just so paralyzing that we are often forced to oversimplify and offer blanket recommendations. It's such a tough job being an informed patient or an informed doctor!
Excellent! And yes all doctors love for their patients to quote any journal. 🙄 But we do have to be more collaborative while trying to educate and I’m down for that. I’m in the group that is low risk for heart disease so far and I do all the lifestyle things. But my cholesterol is creeping up. I’m resisting taking a statin and my PCP isn’t pushing yet.
Agreed, and you know the risks/benefits/highs/lows of self-education. It can be great for patients, and generally I encourage it as part of that collaboration you're talking about. But for patients and providers alike, the bottom line consensus guidelines that experts labor over are essential for primary care docs especially, as we shouldn't be expected to be masters of every study out there. Synthesis is a gift!
Agree!
I run the AHA calculator all the time to determine if someone needs a statin, and with their flat dose response curve, I always start low. My PCP has told me that most of her patients “age into a statin “— she has a mostly female panel. Women over 50 tend to creep up with their lipids, even with healthy habits.., thanks as always, for the deep dive and thoughtful discussion.
Agreed. Many of my female patients increased LDL after menopause. Not sure if it was age or changing hormones. Many proved responsive to small doses of statins like 5 mg of rosuvastatin twice a week.
Same experience here. And the American College of Cardiology did put out this statement back in 2013... a bit dated but I couldn't find anything more authoritative and recent upon a quick search:
https://www.acc.org/latest-in-cardiology/journal-scans/2013/04/19/16/08/alternate-day-dosing-with-statins
Alternate-Day Dosing With Statins
The following are 10 points to remember about alternate-day dosing with statins:
1. There is evidence favoring primary prevention with statins for high-risk patients. Patients with coronary disease should be treated with statins to achieve an low-density lipoprotein cholesterol (LDL-C) <100 mg/dl and <70 mg/dl for very high-risk patients.
2. While the decrease in mg/dl per mg of statin varies, the linear incremental dose response is similar with each of the statins. The percentage of patients who obtain the target LDL-C level of <100 mg/dl is 70% with 10 mg of atorvastatin, 82% with 20 mg of atorvastatin, and 89% with 40 mg of atorvastatin.
3. The efficacy of intermittent dosing of statins relates to the fact that the duration of the cholesterol-lowering effect of the statins is not related to the pharmacokinetics of the individual drug.
4. Steady-state statin drug levels may be achieved in a few days, but steady-state LDL-C reductions take several weeks to achieve, and after discontinuation, it takes several weeks before the cholesterol level returns to baseline.
5. The cholesterol-lowering action of alternate-day statins is as effective as daily dosing in many individuals.
6. To maintain the same degree of decrease in LDL-C when giving the statins on alternate days, the dose of the statins frequently needs to be increased.
7. Alternate-day statin administration seems to decrease the incidence of its adverse effects, particularly myopathy.
8. The effect of alternate-day statins on its many pleiotropic effects is unknown; thus, the efficacy for reducing cardiovascular events is not established. In small cohorts of patients, atorvastatin 20 mg daily decreases the high-sensitivity C-reactive protein (hs-CRP) by 35% compared to 22% with 20 mg atorvastatin every other day (p = 0.08), and there is no difference when baseline hs-CRP is <1 mg/dl.
9. Alternate-day dosing of statins provides cost savings.
10. Large-scale studies with outcome endpoints and prolonged follow-up are needed to substantiate the hypothesis that alternate-day statins are an equivalent strategy for reducing cardiovascular events.
I do the same - we have a drop down, built in 10 year risk calculator in Epic that does provide a quick point of care discussion point... but like you said post-menopausally we really see the cholesterol numbers climb in women, despite no major changes in diet/lifestyle. I'm guessing this and a host of other estrogenic effects that fade away explain how women's CV risk catches up to men in about 10 years after menopause. Thanks for stopping by, Jan :)
Yes, but...
When my father was taken off of statins, he improved within days. Aches diminished. Strength increased. So the question from this anecdote is: How can one figure out that a specific person isn't well-suited for statins therapy?
Yes, but...
Are there any data about blood lipid levels being affected by getting Covid? Whether you answer or not, that's something I'll be asking my own PCP in a few months. Sometimes asking a question with no clear answer, or getting an answer you don't expect, is quite useful.
Hi Jerry - Yes, but... I agree there is never a one-size-fits-all answer or experience with medicines. If someone stops a statin, feels better, then restarts it and feels worse, then stops it again and feels better - you really have to take them at their word! Of course this is not a blinded experiment, but asking a person to set up their own double-blinded placebo controlled self testing is just not reasonable :)
And the answer with Covid seems to be always, "Yes, and..."
You name it and Covid can mess it up, including cholesterol metabolism:
https://www.thelancet.com/journals/landia/article/PIIS2213-8587(22)00389-8/fulltext#:~:text=The%20authors%20found%20increased%20LDL,had%20a%20positive%20COVID%20test.
Hate this disease, hate it. As much as Putin. Sorry my wife just told me he's threatening Finland now.
Great summary of the issue. I'm a big statin advocate but always inform patients up front of this increased risk of DM (and myalgias). it's important also discuss the nocebo effect and the widespread misinformation about statins on the inter web during the opening statin conversation.
The DM risk has been troubling me for the last 5 years and with this latest meta-analysis (of good RCTs) it has accelerated my tendency to offer adding ezetimibe to 10 mg rosuvastatin versus bumping rosuvastatin to high-intensity levels (20-40mg) when seeking additional LDL/apo B lowering.
These approaches have similar LDL lowering power but less myalgias and DM risk with the combo.
I was hoping you would stop by, and I'm relieved that you find this a great summary, phew!
Your strategy here makes great sense. I think it dovetails with the ACC guidance on this in general, although I know as an individual practitioner you are in the zeitgeist:
https://www.acc.org/Latest-in-Cardiology/Articles/2022/08/08/12/27/NLA-2022-Definition-of-Statin-Intolerance
I don't use a lot of Zetia because the outcomes data remains kind of weak, right? But makes sense as an add on or alternative with the statin side effects, dose dependent risks, etc. Thanks again!
I also appreciate this! Great to have an evidence-based and helpful medical professional community here on Substack... there is a lot of the opposite here, too. I'm building a network of trusted sources.
Thanks for this great nuanced review, Ryan! My doctor has suggested statins for me based on my high LDL-cholesterol. I have batted that away since I’m young, do high intensity exercise and strength training 3-4 days a week, and don’t smoke. However, I’m reading “Outlive” by Peter Attia now and he makes similar points about the cumulative longterm effects of high cholesterol and the importance of preventing plaques looooong before there are signs of heart disease. On the other hand, diabetes runs on my mom’s side and my fasting BG chronically runs a few points high (although my A1C is chronically LOW, and I have not been able to reconcile those discrepancy facts!)
What do studies show about the impact of statins on *all cause mortality* for patients with and without diabetes? That data would seem to get around whether or not the marginal added risk of hyperglycemia makes a significant difference
Hi Eric! Thanks for the case study here, and I am also slowly working my way through "Outlive". Very slowly! In general he is way aggressive, and makes some conjectures and best guesses... but they do sound intuitive in terms of looking at a 20, 30, 40 year time horizon. Nothing replaces diet, exercise, etc but the argument for statins over the long term before cardiovascular disease is present makes intuitive sense. Wish there were more studies to prove this. Some people hedge their bets with low dose rosuvastatin most days of the week, maybe alternate day dosing for example. But with diabetes the outcomes data definitely favors starting a statin, such that it is really standard of care. More information than you need but I'll copy and paste from UpToDate:
Lipid management — Lipid abnormalities are common in patients with diabetes mellitus and undoubtedly contribute to the increase in risk of ASCVD. The ADA recommends screening for lipid disorders at the time of diabetes diagnosis, at an initial medical evaluation, and every five years thereafter if under age 40 and annually if indicated, as is usually the case in patients age 40 and older [20].
We and others recommend lifestyle intervention (diet, weight loss, increased physical activity) to improve the lipid profile in all patients with diabetes [20,66].
●Primary prevention – The ADA recommends the initiation of at least moderate-intensity statin treatment for all adults with diabetes between the ages of 40 and 75 years [20]. For patients without additional ASCVD risk factors and a baseline LDL cholesterol close to target, we individualize the decision to initiate statin therapy. This decision can be informed by use of an ASCVD risk calculator. (See "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults: Our approach", section on 'Estimate ASCVD risk using a risk calculator'.)
For individuals aged 40 to 75 years with diabetes and at least one additional cardiovascular disease risk factor, the ADA recommends high-intensity statin therapy with treatment targets of an LDL cholesterol <70 mg/dL (1.8 mmol/L) and a reduction from baseline LDL cholesterol level of at least 50 percent. For individuals with diabetes aged 20 to 39 years or >75 years, the decision to initiate statin therapy should be individualized. For adults with diabetes aged >75 years in whom statin therapy was initiated previously, treatment continuation is reasonable. Approaches to lipid-lowering therapy in individuals with diabetes may vary, and ADA recommendations differ from those of other society guidelines. (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease", section on 'Diabetes'.)
●Secondary prevention – In patients with clinical ASCVD, high-intensity statin therapy should be added to lifestyle intervention regardless of baseline lipid levels. The ADA treatment targets include an LDL cholesterol <55 mg/dL (1.4 mmol/L) and a reduction from baseline LDL cholesterol level of at least 50 percent [20].
Thanks for the detailed info, Ryan! That all makes a ton of sense. I am still trying to wrap my head around fasting hyperglycemia with low A1c (maybe poor sleep? stress?) but according to the ASCVD calculator you provided my risk is quite low and a statin wouldn't be recommended by current guidelines. I can chat more with my pMD at my upcoming annual physical this summer 👍
I agree with your basic take on Outlive, and I will be publishing a book review on it in a week or so. He is definitely aggressive and suggests things that I doubt insurance would cover, although some of those recommendations that would have been considered "aggressive" when the book was written a couple years ago are already becoming mainstream, like pushing colon cancer screening earlier than 45. I am overall impressed by his rigor of analysis of the literature, and unlike many quacks out there he constantly talks about EBM concepts, NNT, absolute vs risk reduction, trade-offs, uncertainty, etc. He is also refreshingly frank about the limitations of EBM and doesn't fall into the trap of pedantry like VP and the SM crowd, screeching "BuT ThErE's No RCT FoR ThiS!!" even when it is a low-risk intervention for which that type of study could not be easily or ethically done. He also walks a fine line of being neither a shady product/supplement hawker nor going full "alternative medicine" and bashing pharmaceutical interventions.
Whether some of his approaches are borne out by longitudinal studies remains to be seen, but I think his work through his book, podcast, and other activities are making a huge beneficial contribution in three ways: (1) focusing on prevention rather than reactivity, (2) trying to improve QUALITY of life as much as or more than QUANTITY (I actually think "Outlive" is a bit of a misnomer for his actual views), and (3) placing the biggest emphasis on lifestyle interventions medicine has largely neglected until recently, like diet, exercise, SLEEP!, and emotional health / stress management.
Such a good review, and I will look forward to reading your actual post... although you could save yourself some time and just cut-and-paste this excellent comment!
I need to find the time to read the rest of his book, but that pesky sleep notion keeps creeping in. I'm struggling to hit those 7 hours, but mostly getting at least 6 which is not great.
I'm reading the diary of Ann frank right now in preparation for a trip to Amsterdam this summer. I saw one of your notes that you might have just been there? I'll try to catch up on everything tonight/this weekend... and read more Attia on the plane soon. He also comes across a bit arrogant, speaking as a former surgeon who claims to have been disillusioned by the reactive practice of medicine, and like he's the only guy in the room who thinks of reframing medicine 3.0 around prevention... maybe he could have taken a severe pay cut and joined me in the trenches of primary care, where most of us primary docs happily serve and do counsel about prevention ALL THE TIME!
Thanks for stopping by :)
Sorry I also meant to give this a sincere ❤️ and 👍
“ He is also refreshingly frank about the limitations of EBM and doesn't fall into the trap of pedantry like VP and the SM crowd, screeching "BuT ThErE's No RCT FoR ThiS!!"
Interesting you write about this today, as yesterday I had a long overdue lunch with two friends, a retired nurse and a truly extraordinary NYU prof of PT who has helped both my nurse friend and me enormously. The question as to whether and when to take statins came up. They both observed that, despite excellent exercise and nutrition regimes, which they both have—I’m decent, but not by any means in their league—it seems inevitable that, as you age, LDL goes up, and then the question is what to do about treatment and when. They both agreed existence of more than minimal level plaque was an important criterion (about which I learned first from you and from commenters on one of your earlier posts). The PT Prof also continues to find the ratio of HDL to overall cholesterol, 3.5:1 being optimum, if I remember rightly, a useful indicator. I am curious about any thoughts you might have on the whole set of possible indicators, and particularly the ratio, as I don’t see that referred to as much these days.
Hi Susan - very good points, and the nuances regarding statins will continue to be teased out, debated, and weighted for many years. But on the whole, for people with higher risk problems and lifestyles, the benefit seems clear, and the overall risks low. Family history is kind of an X factor that doesn't make it into a lot of the calculators, as they pull from studies like the Framingham study that did not have reliable family history data to mine (my understanding). The addition of the coronary artery calcium scan (CAC), usually paid for out of pocket for maybe $150, can add some real evidence for who is actually laying down plaque and therefore a great candidate for statins. The Skeptical Cardiologist (commented above) has some excellent articles on this!
Oh, yes, it was the Skeprical Cardiologist I was thinking of. He has really useful information—although sometimes over my pay grade, I learned a lot from hi, as I do from you!
*Skeptical, not Skeprical.
Brilliant, thank you!
"Kind of. Not really. Sort of." That's unfortunately all the time (and perhaps knowledge) many primary doctors have to break this stuff down. Appreciate the expanded conversation here!
I would also add that HBA1c stands for "hemoglobin A1c" and is used to estimate average blood sugars over the past 2-3 months, right? What are the normal/diabetes ranges? Above 6.5 is type 2 diabetes still?
Hi Grant - and I'm sure I'm guilty of this kind of short hand when running 40 minutes late and tending to some patients with problem lists into the 30's! But I try when I can to expand the dialogue and meet people where they are... this post might have been built upon too may assumptions, like HBA1c being a familiar concept. But you got it - <5.7 or so is normal, 5.7 - 6.5 is pre diabetes or impaired fasting glucose, and >6.5 is the agreed upon definition of diabetes. There is a continuum of risk that goes up with the HBA1c, but the 6.5 number is the inflection point where significant complications like diabetic retinopathy really start to develop over time. Kind of. Sort of ;)
Thank you for this column Ryan!
5 years ago, at age 63, my total cholesterol bumped just above normal on yearly labs, triglycerides & HDL normal. My doctor put me on Rovustatin, telling me, "you have a great risk of having a heart attack or stroke within the next 10 years, without it". After a couple of months my legs began to feel like they were going to sleep, so I went back to her. No other statin was suggested. She was my doc of 8 yrs. & once told me that "I am the Dr. & you are the patient" & to just take the statin, which felt pretty crappy at the time for this older nurse. I had questioned her about how people could take a statin & feel this way. So I stopped it & didn't see her again before I retired & we moved to the NW.
New PCP here noted that my LDL went up "quite a bit" , which was higher after quitting the Rovustatin for a year. He hadn't seen the years of normal cholesterols. He started me on Atorvastatin, which I tolerated for about a year & then, last month, my new PCP, a DO recently out of school, tells me on the 1st visit that, "the statin will not benefit you". I had just started having the leg pain, now also with a rash on lower legs. Both gone after 2 days when I quit taking statin after that visit. I see him again in 6 months. Glucoses had been creeping up & had been normal before statin.
I'm 68 now, retired 3 years ago from a long 45 year ER nurse career.
Now, work with a trainer & work out 4 days/week. I eat now & have to work to get 1800 cal a day in... increased water intake, starting in the morning. I'm also now able to sleep, go to yoga class. I feel great, take very few medications after living on Advil for years. Joined the Garden club & Soroptimists. BP rarely up, almost zero migraines after 10 a month for years. The CAC is a test that I would pay for, but what then?
I'm grateful just to have a PCP, as we seem to be in a bit of a medical desert here for boomers, with providers coming & going while employed by 1 of 2 hospital systems in the valley.
I'm always open to less medications & doing what I can to improve my chances of being around a number of more years to enjoy the grandkids & life.
Thanks again for this one!
Hi Nurjam - and thanks for this comment, it is really instructive. This one had me cringing!
"I am the Dr. & you are the patient"
Eww!
There is a definite psychology to taking medicines, and with statins in particular we tend to back off the healthy behaviors thinking the medicine has us covered... but like you said there is no substitute for the hard work of eating well, exercising, and all the rest... which end up making us feel much better anyway! Unless we are like the millions of folks with long Covid post-exertional malaise or other medical problems wherein exercise is not great/possible. I'll keep exercising and eating fairly well with you as long as I can, and I'm glad you have a PCP. The field has been decimated and neglected lately, with up to 30% of docs leaving since the pandemic I think, and a big shortage of residents in training. Thanks for stopping in :)
Thank you Ryan, This info was timely for me. I was recently started on a statin. My Hb A1c was borderline for pre diabetes and both my parents had diabetes. A CT done for a different reason did show some atherosclerosis of my abdominal aorta ( not surprising at age 72). So despite a low BP and no personal cardiac issues a statin seems a good choice. I will continue diet and exercise efforts. Marty
Thanks Marty for sharing, and I think your choice is a good one, with lots of evidence that statins help reduce risk when atherosclerosis is detected regardless of our obsession with LDL. I know you'll keep up with the diet, exercise, stress reduction, and California state of mind which all combine to be more important than the statin. Let's hope for a calm November, and better times ahead for the world. Let's chat soon and I'll share what "we" are doing re: statins lately, too ;)
Great story!
I do like patients to advocate for themselves but too many are not equip to understand the nuts and bolts of studies. Instead they rely on MSM and anecdotal 'information'. This is a nice article. https://www.medicalnewstoday.com/articles/safest-statins#summary
Bottom line, no therapeutics without risks. Maybe a printout would help.
So true, KB, thanks for adding this. Actually one of my patients ( a reader) told me today that a lot of my articles have become a bit complex for her lately. So hard to strike a balance between writing about stuff on a different level than people can get from your average "medical/health newsletter" and getting too wonky. I'll have to throw in some more quick ones soon for her at least :) And yes, nothing without risks - always weigh risks, benefits, alternatives.
Yes, even ‘natural’ carries risks as well.
Thanks again for a great column. I think it's really important to stress that for secondary prevention, there really isn't a question about benefit outweighing harm. When I was a resident in the hospital I trained at, which is the largest hospital in the state and the main stroke centre, I managed I managed to get lipid profile taken off the "routine" bloods done post ischaemic stroke by pointing out the futility of doing them soon after a stroke, and also that it wouldn't change management. Mind you, this was in the days before PROVE-IT and PCSK9 inhibitors! I also recall having arguments with the cardiac nurse for refusing to order lipid profile in ACS patients for the same reason. They complained to the attending who happily agreed with my reasoning.
When it comes to primary prevention, the rationale can be far more nuanced, but I often have little time to delve into the nuances since they're usually not there to see me for that! If only we had more primary care doctors like you Ryan!
For what it's worth, my usual go-to is pravastatin since I have the impression it actually led to improved glycaemic control in the trials, and I think I've seen some advertising/opinion that pravastatin also isn't bad for glycaemia, though it is not widely used at all in Australia. There have been observational studies suggesting that lipophilic statins might lead to worse outcomes in PD, so I often such l switch my PD patients to hydrophilic ones, and there is also a risk of reversible cognitive impairment with the lipophilic ones, so worth keeping in mind if you have a patient with cognitive issues on a statin.
Very insightful and helpful comment, thank you! Totally agree with primary versus secondary, and questioning whether a test will change the plan is important. Agree with lipophilic statin preference, and need to give pravastatin more respect. We are pretty into rosuvastatin here…