Thanks David for the detailed explanation. It provides important context.

I am a Cardiologist/Cardiac Electrophysiologist currently in private practice in a college town in Georgia. I was at University of Florida Jacksonville before that. I met Robert Cywes about 20 years ago when we were both at Baptist Hospital, Jacksonville. I reconnected about a year and a half ago. I’ve been LCHF for 2.5 years and have lost a lot of weight. I consider Robert Cywes and Eric Westman my mentors. I have been a member of SMHP since 2021, just missed being a founding member, I’m also in the FLCCC. I did training with Nutrition Network and am applying for certification at SMHP now. Honestly after four board certifications, more letters after my name is not nearly as important as the new insights I have gained with ketogenic medicine. Though I am primarily an EP I do a lot of heart failure and Nuclear Cardiology. I would be more than happy to share any of my insights with you. Robert keeps threatening to interview me for his channel. I will do it but I cannot publicly show too heterodox a viewpoint. I do not want to irritate my partners or referring physicians. I would like to comment though on the rapid progression of CAD “BS” abstract from Circulation.

So, to start, you pointed out correctly this patient was not a true LMHR. He had a previous PCI of his proximal LAD, almost certainly with a stent, probably drug eluting, making in-stent restenosis less likely. The implication was that previous intervention was elective and not associated with an event (STEMI or non-STEMI). Subsequently he had 2 years of statins, protocols would suggest 40-80 mg of Atorvastatin, confirmed by the authors, for two years with a subsequent unknown period of no statins and then on a “strict ketogenic diet”, which the authors probably cannot define. They also mentioned that the previous catheterization showed only moderate disease in the distal RCA. This generally means 40-60%, not enough to cause significant ischemia. LDL was implied at “target”. The goal posts keep moving. Previously it was <70 mg/dl, then it became <50 and now with PCSK9 inhibitors like Praulent (I hate generic names, it is not as if I will prescribe them more often) the target is <40. Some even talk about getting LDL into the 20’s, the same as an infant! They got him down to 14.

Now for the STEMI (ST Segment Elevation Myocardial Infarction). This means there is at least a transient if not permanent occlusion of a major vessel causing an ST segment elevation on EKG. In this case the RCA (Right Coronary Artery) Interestingly, but not uncommonly the vessel is open by the time the patient reaches the cath lab. This can be because of innate thrombolysis by native TPA (Tissue Plasminogen Activator), or the combination of drugs such as high dose aspirin, Plavix like antiplatelet agents as well as heparin. Had the disease progressed?, from moderate distal RCA disease with no mention of the more proximal RCA disease which most likely previously existed, to 95% mid RCA and 99% (subtotal) distal RCA stenosis. This is NOT what it may seem. First these are visual estimates and not measured values. Generally, angioplasties are done first to proximal lesion to reestablish proximal blood flow and if there is any thrombus shed distally to the second lesion which is now protected by a wire so a second balloon and stent can be placed. Both clot and atheromatous plaque are pressed into the vessel wall, and you are done, sort of. With such high grade stenosis in the setting of an acute MI with partial recanalization, normally a wire is advanced and then with an appropriately sized stent loaded out of the box is advanced and deployed. Measuring flow with either iFR of FFR is not usually done in the setting of acute MI. The stents are very thrombogenic and generally require two antiplatelet agents for 6 months to a year. The stents are coated with an anti cell growth agent to prevent scar tissue from growing inside the stent and re occluding it. The drug coating is frequently Sirolimus aka Rapamune, yes a rapamycin analog. MTOR yet again.

So how did this STEMI occur, and did his CAD really progress rapidly? The simplest and therefor most likely explanation is that there was some mild mid RCA luminal irregularities, not usually reported at the time of the original LAD intervention. This single lesion easily even with statins could have progressed to a 30% lesion over several years. MI’s, especially STEMIs usually occur when a mild, 30-40% lesion that has an unstable plaque ruptures. Thrombus now forms and occludes the vessel causing a STEMI. If the patient is fortunate enough the occlusion which is partially if not mostly thrombus will partially dissolve and open up a small channel restoring some blood flow and terminating the MI. Frequently thrombus from the initial insult will flow downstream and partially or completely occlude the distal lesion which still could have been moderate in this case. The 99% distal lesion could be 60% plaque and the other 39% downstream clot. There is no way to tell and more importantly it does not matter since you treat it the same way with primary angioplasty. You want to reestablish as much blood flow to the heart as soon as possible to minimize long term damage. This is the crux of the statin argument that you will stabilize the mid RCA 30% soft non calcified plaque, suck out the lipid stabilize it with calcium, thus increasing calcium score and theoretically preventing the MI. You cannot tell if the 95% mid and 99% distal stenosis were plaque or clot. The day of his MI he may have only had a 30% mid RCA lesion, barely worth mentioning in the initial cath and a stable 40-60 % distal lesion. There is no need for rapid progression and absolutely no evidence for it either. I have not even mentioned his elevated Lp(a) which is significantly elevated and could have in itself caused a thrombus that occluded my proposed 30% mid RCA lesion. Again, with no significant progression of CAD.

Lp(a) on an Apo B competes with plasminogen for Tissue Plasminogen Activator (tPA), mentioned previously. Activated plasminogen is thrombolytic, thus the more Lp(a) the less fibrinolysis and the greater the likelihood of spontaneous thrombus. The more Kringle IV repeats on Lp(a), the more thrombogenic it is. His level was 155 nmol/l. Anything over 125 is considered very high and a significant risk. Niacin and PCSK9’s can lower Lp(a), but not much else. Orthodoxy believes Lp(a) brings cholesterol to damaged endothelium and promotes athrogenesis. OK possibly. Lp(a) attracts inflammatory cells to vessel walls and can lead to smooth muscle proliferation. It also may be involved in wound healing by delivering cholesterol to the endothelium, a good thing.

Lp(a) does something bad, but I don’t think we have a complete mechanism.

So that’s my take. No firm evidence of rapid progression of CAD. His pre-STEMI lipids from our perspective are not bad (Chol 388, LDL 301, HDL 73, TG 71) and he has a near 1:1 TG:HDL ratio.