The Straw That Breaks the Camel’s Back: “LMHR (Lean Mass Hyper Responder)”
Case Presentation:
A 63 year old recently retired first responder is brought in by life flight helicopter from a nearby ski mountain after suffering out-of-hospital cardiac arrest while skiing with his wife. Fortunately, a Ski Patrol witnessed the event and performed outstanding bystander CPR and he was able to be intubated and taken directly to the cath lab where he was found to have severe diffuse 3-vessel coronary artery disease.
He spent a few days in the ICU and was able to be extubated, neurologically intact (no brain damage).
The workup in the ICU revealed that his LDL-C was 250mg/dL, suspicious for a diagnosis of Heterozygous Familial Hypercholesterolemia.
Given the severe and diffuse nature of his disease, a 5-vessel bypass operation was recommended along with intense medical management, to include high intensity statins and more.
He was eager to undergo the bypass operation but adamantly refused to take statins. His wife supported him in this stance, declaring “we don’t take statins in our family!”
They had been following some influencers on YouTube and “X” (formally known as Twitter) who had convinced them that statins were evil and high cholesterol was necessary for optimal health. They had been following a “Carnivore” diet for the last 5 years.
He underwent coronary artery bypass grafting (CABG) and his hospital course was extremely complicated and rocky - requiring several more weeks in the ICU, eventually making it out of the hospital, only to be readmitted several more times over the course of the next year for heart failure and heart rhythm complications.
Flying Under the Radar
You just never know which inflammatory trigger, from which infiltrating LDL particle is going to be the one that causes that red hot “pimple,” or plaque to rupture and spew it’s gooey contents into the arterial lumen, activating platelets, clotting factors and forming a massive sticky thrombus that instantly plugs the pipe (coronary artery).
In atherosclerosis, LDL is largely what is causing the inflammation - the repetitive infiltration of LDL particles into the intimal layer of the vessel, every second of every day. As inflammation progresses, the architecture of the plaque becomes less and less stable over time, until one day it bursts, like a “zit” on a teenager’s face. If that happens high up in the “widowmaker” artery (Watch The Widowmaker | Prime Video) called the LAD (left anterior descending), a large amount of myocardial tissue living downstream is suddenly deprived of blood and oxygen. This causes ventricular fibrillation (V-fib arrest), where the heart is no longer squeezing or pumping blood, and the person dies instantly.
Nobody wants that for their loved one. Certainly nobody dispensing advice on social media should want that on their conscience.
Nothing that raises ApoB is likely a good thing.
“This explains the failures of therapies that raise ApoB, including fibrates and DHA” - Dr. Matthew Budoff, MD @BudoffMD - “X” 2/2/2023.
ApoB represents all atherogenic particles, but LDL is by far the predominant player in atherogenesis. LDL-C is the biomarker for LDL.
As we discuss elsewhere, atherosclerosis takes many years (decades) to develop. The risk of atherosclerosis is commensurate with the cumulative exposure to atherogenic particles.
With the latest diet craze invoking a ketogenic diet and lifestyle as the panacea, or “therapy,” for all one’s ills, there has been an epidemic of LMHR patients arriving at the preventive clinic with, sometimes, astronomically elevated LDL-C levels. This is not likely a good thing, but it largely depends on baseline risk and exposure time to such high levels.
We presently don’t have enough data to inform us on the hazards of this particular dietary impact. Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: A scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force
What we do know is that LDL is causal to atherosclerosis and casting doubt and misinformation about LDL causality IS harmful.
If, after reading this document, you feel the benefits of a ketogenic diet outweigh your individual risk for future ASCVD and you wish to engage in this lifestyle, please consider our checklist below:
CardioAdvocate Checklist:
Talk to your doctor, ideally before initiating a ketogenic diet
Begin a formal risk assessment based upon established ASCVD risk factors and available risk calculators
Obtain baseline lipid panel
Assess Non-HDL-C or ApoB if triglycerides are elevated (typically > 150 mg/dL)
ApoB may be assessed at baseline and with changes in diet, lifestyle or lipid lowering therapy. This is typically a separate blood test
Check Lp(a) - blood test
Lp(a) is another atherogenic lipoprotein causal to atherosclerosis
> 125 nmol/L (50 mg/dL - less preferred assay) - associated with heightened risk of premature ASCVD, often presenting as heart attack or stroke
Coronary Artery Calcium Score A Picture is Worth a Thousand Words - Coronary Artery Calcium Scores
Age > 40 years with at least 1 risk factor
May consider screening at younger age if other significant risk factors present such as family history of premature ASCVD
Follow up with doctor
Repeat lipid panel with ApoB after 3-6 months or with any other significant lifestyle or clinical changes
Periodically thereafter, at least annually
Deep Dive
Lean mass hyper-responders (LMHR) refers to a specific phenotype with lower BMI, total cholesterol > 200 mg/dL, HDL-C > 80 mg/dL and TG < 70 mg/dL. Many followers of this ketogenic diet purport this to be a cardioprotective diet. The near fanatical obsession with this lifestyle has fueled a vociferous following on social media, with the unfortunate and in our opinion, reckless consequence of spreading doubt and misinformation about the causality of LDL with atherosclerosis.
This has led many high risk patients to shun the very therapy which may save their lives. Providers spend countless hours of precious time with their patients unraveling this misinformation before they can even begin to address their ASCVD risk. Unfortunately for some, we just never get to that point. It’s 45 minutes into the clinic visit and the patient remains unconvinced. Both give up.The patient leaves frustrated and the provider is one step closer to “provider burnout” and yet another example of “the straw that breaks the camel’s back.”
For the sake of validating and elevating their chosen lifestyle and obsession, above all others, these self-proclaimed and uncredentialed “lipid expert” influencers have taken their passion to a dangerous level. Instead of advocating for personalized risk assessment, they have gone down a rabbit hole (speaking of rabbit’s, here is a reference to the historical landmark study Anitschkow study in atherosclerosis: Nikolaj Nikolajewitsch Anitschkow (1885–1964) established the cholesterol-fed rabbit as a model for atherosclerosis research - ScienceDirect) of trying to prove that LDL is not causal to atherosclerosis. Heart disease is the #1 killer in the US and developed nations. LDL causality is without question. They have chosen to not only pick a fight with one of the most fundamental of scientific facts, but they have chosen a disease so deadly, that their misinformation is tantamount to screaming “fire!” in a crowded theater, but on a global scale. The harmful consequences of this cannot be understated.
LMHR influencers conflate baseline low risk and the lack of noticeable impact of transient exposure to very high LDL as “proof” that LDL is not causal to atherosclerosis. Many of these influencers are relatively young and have a baseline low risk. But they have no idea about the baseline risk of the general audience they are preaching LDL misinformation to. As detailed in the “Widowmaker” documentary (Watch The Widowmaker | Prime Video) and in this study (Preventing myocardial infarction in the young adult in the first place: how do the National Cholesterol Education Panel III guidelines perform?) there can be absolutely zero warning signs and few underlying risk factors for the majority of “younger” victims of their first heart attack. It’s one thing for an individual to balance their personal risk, but it’s quite another to proclaim LDL not causal to atherosclerosis and encourage wide swaths of individuals to adopt this potentially harmful “therapy.”
It’s ok to hypothesize about lesser known areas of science and medicine. It’s also ok to question long held beliefs and tenets of science and medicine. There are appropriate forums for this. It’s ok, at times, to accept a particular therapy for one individual, which may appear harmful to another. Medicine isn’t perfect. Not every individual, in every situation has or will be studied in a randomized controlled trial (RCT).
But it is not ok to categorically deny or refute therapies proven to be effective in an effort to discourage their use to patients who would benefit. Nor to systematically encourage the administration of therapies which are more likely to cause harm. A physician who routinely engages in such practice patterns would put themselves at risk of malpractice and litigation.
It is our opinion that influencers on social media who engage in spreading misinformation and are routinely advising patients against Class I recommendations and/or are routinely promoting Class III recommendations are either committing malpractice (if clinicians) or impersonating a clinician who is. Such influencers ought to be held accountable for their potentially harmful actions and called out by the medical community.
There is a safe way for individuals to choose a particular dietary lifestyle that works for them, including ketogenic. And let’s be clear, dietary studies are incredibly tough to perform and they do not produce robust Randomized Controlled Trial data to guide us. The best diet is the one that an individual can stick to. Therefore any diet study is confounded by the simple bias that ANY diet adhered to will often produce better results (weight loss primarily) than NO dietary strategy.
A diet which significantly raises LDL particles, however warrants scrutiny and deserves to be closely evaluated and studied. Individualized baseline risk needs to be assessed and adverse effects need to be monitored.
There is sparse data on the long term effects of ketogenic diet, particularly on LMHR. Studies are ongoing (Lean Mass Hyper-responder Study – Citizen Science Foundation) and spearheaded by Dave Feldman (@realDaveFeldman) / X with Dr. Matthew Budoff (@Buddoffmd) as principal investigator. This study is designed to track plaque progression by Cardiac CT imaging over a period of 12 months, but following 2 years of exposure to high LDL-C on a ketogenic diet. This will certainly be of interest, but again, will largely depend on baseline risk and adequate power to detect a significant change, based on that risk. If patients are low risk at baseline, exposure may not be significant enough to demonstrate a difference on CT. If not enough higher risk patients are enrolled, we may not have an answer to the question of whether “X” period of time on a ketogenic diet with “X” increase in LDL-C results in “the straw that breaks the camel’s back” in high risk patients.
Here is a link to a review done by the National Lipid Association (Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: A scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force)
