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Atherosclerotic cardiovascular disease (ASCVD) is one of the few chronic diseases for which we have a clear, causative factor that can be targeted therapeutically to reduce long-term risk. The strength of evidence from genetic, randomized, and observational data all points in the same direction: ASCVD is caused by circulating, cholesterol-carrying, apolipoprotein B (apoB)-containing lipoprotein particles, which above certain threshold concentrations have the ability to leave plasma, pass through the arterial endothelial lining and enter the underlying intima layer, where atherogenesis occurs. Reducing apoB particle numbers can thus drastically slow disease progression. Of the various pharmacological treatments now available for reducing circulating apoB particles, one of the earliest classes of drugs to be developed remains one of the most effective (and affordable) options – statins.
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It would be nice to have the studies used for the articles… NNT can vary depending on the study. (When talking about statins, it may help to mention about levels of CoQ10.)
So which statin do you choose in patients with pre diabetes?
Thanks as always for this amazing distillation!
Sarita Nori MD
Thank you for this excellent article. I understand that there is no serious doubt that lowering ldl cholesterol lowers one’s risk of ascvd. But there are some studies that seem to show that lowering ldl too far may increase all-cause mortality. For example: https://www.bmj.com/content/371/bmj.m4266#:~:text=Conclusions%20In%20the%20general%20population,(140%20mg%2FdL).
In that study, even among statin users, the “best” ldl-c level, from an all-cause mortality point of view, was 89, not lower. Is the study flawed in some way? If not, what is your best guess as to why all cause mortality may rise even though ascvd risk decreases as you reach very low ldl levels?
great analysis.. thank you!.. I’m 75, great health and have been on statins for probably 20 years now, initially on Pravachol then my doctor switched me over to 40mg of Atorvastatin… two years ago he raised that dose to 80mg/daily stating that the cardiologists at Harvard Med School (where he teaches) now believe you should take as much as you can handle. My most recent LDL was 66. I have had no noticeable side effects from any dosage of a statin.
What is your take on the Harvard comment? And you focused almost exclusively on LDL… what about HDL and Triglyceride counts? Appreciate any info you can provide.
Terrific Information!!
John
Good understandable info.
Powerful stuff. I just got my ApoB result back and was alarmed that it was 104. I’m making some drastic dietary changes and will retest again in 6 months. If it’s still above 80, I’m going on a statin. My doctor laughed me off since I’m “only” 29, but ASCVD is not something I want to mess around with. Thanks Peter.
I’m a chiropractor and have seen one case of rhabdomyolysis associated with statins in 25 years of practice. In addition, a dozen or more cases where the patient was certain statin use caused them to develop Type 2 diabetes. That’s in keeping w/ the reported unwanted effects of statins. That said, after listening to your podcasts over the last year and your use of logic in this article, I’m convinced of the efficacy of statins and much less concerned about the unwanted effects. THANK YOU!
Not knowing much about ASCVD before now, it was very illuminating to learn the overall rates of cardiac death in the trials in the table.
That 3.3% reduction seems not so substantial because it’s not clear what the baseline is. In the 4S study, it’s the difference between 11.5% of subjects dying in the control arm and 8.2% dying in the statin arm. The non-coronary deaths were around 2.3% of all patients in both arms.
The hazard ratio of .7 is perhaps an easier way to look at it from the view of an individual, in that you can lop off 30% of your chance of death, according to the way a statin was used in 4S.
This sort of risk evaluation has of course been covered elsewhere on this site, but it’s really hard to look at a single risk number and get a feel for the difference in two arms. You need to know both what is the chance of an even happening, and how much is it reduced. A 100% reduction of a one-in-a-billion event is very different from a 30% reduction in chance of a one-in-ten baseline chance.
Great read. Important insight. Thank you Peter
“Several alternative therapeutic options to statins – such as PCSK-9 inhibitors or bempedoic acid – are also effective in combatting high LDL.” I’m surprised that you didn’t include ezetimibe. While perhaps not quite as effective as PCSK-9 inhibitors and bembedoic acid, it’s much, much cheaper and also often prescribed in addition to a statin.
Excellent synopsis! Thank you.
Thank you, Dr Attia. Very good summary and we need to fight for interventions that will prevent CV disease. I think statins are the original and best proven Longevity medication.
Any thoughts on nutrient depletion? Specifically Coq10? Kind regards.
Thoughts on statin therapy in someone that uses prednisone 2-3 times per year for lung disease? Not prediabetes but probably closely approximates
very informative – do you have an acceptable range level for Apob? (hello, medium, high) and if one has a calcium score say greater than zero – say under 20 which seems low – does not matter greater than zero trumps a low Apob? Didn’t see calcium score mentioned.
Why is apoB not an automatic requirement on every standard blood test?
Was prescribed a statin. After two months I began experiencing muscle & joint pain. After reading about the possibility of muscle damage, I stopped. Approximately four months past before the pain disappeared.
Listened to Rogan’s discussion with Dr. Molholtra about an alleged under reporting of the incidents of muscle damage from long term use of statins.
Is he one of the critics you reference in this article? Thoughts about his position?
Does smoking and hypertension have a direct effect on apoB levels, or are they thought to play a parallel position with inflammation or vascular wall changes? I’m not quite ready to say apoB is causal. Yes, it’s a reason for ASCVD, but it seems like there are many reasons for ASCVD with apoB being perhaps an important ingredient, but ASCVD still appears to be a Western malady associated with a Western lifestyle. Okay, statins will work safely, but are we supposed to stop there, order the pill without further curiosity? Sure, doctor appointments aren’t equipped to address our culture, but other things are happening here. Other new things and in significant amounts: sugar, vegetable oils, white flour, screen time, creature comforts, the list is long, but whatever happened, it apparently happened over the last century or two. Cigarettes and the volume of cigarettes are nasty, sure, but they are also confounders, along with many industrial age confounders. Has the DA found evidence and made an arrest, without any interest in others found at the scene of the crime? Awesome article, very informative, I loved it, but I remain curious.
My LDL and total cholesterol started to exceed the acceptable range in my early 40s, but since my total/HDL ratio was “good,” my doctor didn’t see any cause for concern. After listening to Dr. Attia, I asked my doc to order an apoB test along with my annual lipid panel. My insurance wouldn’t cover it under my annual preventative, but it cost less than $25 out of pocket. My apoB came back at 116, well above the “accepted” range of 90, and nearly double Dr. Attia’s data-supported recommendation of 60. I provided links to several studies on the correlation/causation between apoB and ASCVD to my doctor and asked him to prescribe a statin for me. My high deductible “marketplace” insurance is crap, but it covers the cost of 20 mg of Atorvastatin 100%. It is free. No copay. No deductible. In 2 months, my apoB went from 118 to 63 (47% reduction), and my LDL went from 174 to 83 (52% reduction). Thankfully, I’ve tolerated the statin well, with no noticeable side effects. We can’t know what the future holds, but I like my odds better with these new lipid numbers. I’m very grateful for the information on this site and in the podcast. Worth every penny!
Is there a link between low circulating cholesterol and increased cancer risk? If so, how does one mitigate that risk?