This is where the whole “risk-weighted ApoB” enters that we’ve discussed before. This shows superior fidelity compared to just straight ApoB. I would expect at some point for this to become standard on lipid panels in routine primary care. When - who knows, seeing as ApoB which has been validated and available as an inexpensive test for decades, not to mention the more recent Lp(a) is still not the standard in many SOC guidelines.
Risk-weighted apoB: a novel summary metric outperforming traditional lipid biomarkers in predicting coronary heart disease
Thanks for posting but all-cause mortality is not very relevant if we are talking about LDL. For example, someone dies of cancer and has LDL of 20 means nothing. A more relevant breakdown would be CVD death %'s by LDL levels. If there is such statistic, then it would be very meaningful. Don’t know if exist or if you or anyone else (with tech advanced skills) can dig it up. Thanks,
Annualized Incidence Rates (95% CI) by Achieved LDL-C Level:
< 20 mg/dL: 0.89% (0.54, 1.46)
20 to < 40 mg/dL: 1.22% (0.79, 1.89)
40 to < 55 mg/dL: 1.66% (1.03, 2.66)
55 to < 70 mg/dL: 1.20% (0.66, 2.18)
>= 70 mg/dL: 1.30% (0.78, 2.16)
Adjusted P-value for trend: 0.10 (No Statistical Significance)
After multivariable adjustment, the trend across the LDL-C categories for cardiovascular death yielded a P-value of 0.10. Because this value is greater than the standard significance threshold (typically 0.05), the data does not demonstrate a statistically significant linear relationship between lower achieved LDL-C levels and a reduction in cardiovascular death
So much for loading up with muscle killing/aching statins LOL. I’m gonna go every other day on my 2mg’s of Pita and 10mg EZE and that should be enough to keep mine at around 70 mark. My last reading I was at 72 after having done 2mg pita and 10mg Eze daily for four months which lowered my LDL from the 130 level.
So basically, the way I read this is: There is literally close to ZERO benefit for anyone who is
at 70 LDL-c level to go down to a 20 level. Thank you and that’s what I suspected all along.
To be fair I always thought that LDL-c level of about 70 is close enough to optimal, and anything over 90 being as higher than normal.
Having said that people in very high-risk categories probably get some benefit in keeping it at very low levels.
Good info. I’ll act on this. My numbers aren’t bad but not good enough I fear. ApoB of 69 with hsCRP of <0.2 and Lp(a) of 8. My diet is as clean as I can stand it. I’ve been on bempadoic acid and ezetimibe (Nexlizet) for 1.5 years. Last week I started on Repatha ($249 no insurance for 2 injections lasting 2 weeks each). I feel zero side effects so far. I’ll see how far down the apoB goes. It’s been as low as 45 on rosuvastatin 5mg plus ezetimibe 10mg but I couldn’t stay on the statin. I’ll report back in a few months.
Recent numbers: ApoB 69, LDL 56, hs-CRP <0.2, HbA1c 5.5, GGT 12, uric acid 6.3. My apoB was 63 earlier this year so perhaps the 69 up tick is noise (but I’m ready to get more aggressive anyway).
You shouldn’t be getting more aggressive with nothing other than your glucose/HbA1c. Plus an LPa of 8 means you are in low risk category for CVD. No need to overdo it with lipid lowering efforts. The rest of your numbers are just perfect. Your HbA1c should be sub 5.2 always. Mine is 5.2 but I prefer sub-5, ideally 4.8.
Maintaining low HbA1c/FG is the “new cholesterol” LOL when it comes to staying healthy. IMO too much attention is given to LDL-c and too little to FG and HbA1c.
Ah, “perfect”. If only I could be so certain. Every man in my family (generation before me) has died of heart disease. My dad had multiple bypasses before succumbing at 80. With my 64yo heart CAC score >300 I think a bit of aggression is a good bet. You are definitely right about the Hba1c worry. I have long been >5.6 and recently as high as 5.9. I am already on Farxinga. Metformin interferes with my exercise. When I use a CGM my blood sugar estimate is incredibly stable (low with small, short bumps for carb intake) so I’m cautiously assuming my highish Hba1c is an exercise artifact (long lived red blood cells). It’s all a work in progress. Onward and upward, eh?
Oh well that might be the case BUT you did not inherit the kill gene they had LOL. Your superb LPa of 8 is a HUGE green flag for your CVD. Lest they rest in peace (the ones that passed) but you can rest assured that you won’t be joining them anytime soon (given your numbers) as long as you work on your HbA1c and make it move it toward the 5.2 goal, though 5.5 it is not too bad.
I put this paper into Claude (AI) and asked about the limitations. Some of what Claude replied with is listed below:
This is an observational comparison dressed in trial clothing. The randomized part of FOURIER was evolocumab versus placebo. This analysis is something different: everyone in the open-label extension was on evolocumab, and the authors then sorted people by the LDL they happened to achieve and compared the bins. Achieved LDL on a fixed drug is not randomized — it’s driven by genetics, adherence, absorption, baseline LDL, and general health. That opens the door to confounding and reverse causation in both directions. Classically, low cholesterol can be a marker of occult illness (cancer, frailty, inflammation), which would push low LDL toward higher mortality; the fact that they saw the opposite is somewhat reassuring, but it also means unmeasured health differences between the bins could be doing some of the work. They adjusted with a multivariable model and concede residual confounding remains. The upshot: the “lower LDL → lower events” gradient here is an association within a treated cohort, not the randomized causal estimate.
And the randomized causal estimate on mortality is the weak spot of this whole drug class. The parent FOURIER trial, which was randomized, did not show a statistically significant reduction in all-cause or cardiovascular mortality from evolocumab — it reduced MIs, strokes, and revascularizations, but the mortality curves didn’t separate significantly over its 2.2 years. So the strongest mortality reassurance you’re getting from this paper is the observational achieved-LDL gradient, not a randomized mortality benefit. If mortality is your gold-standard endpoint (reasonable — it can’t be gamed by shuffling deaths between cause categories), the honest summary is that the randomized evidence for a mortality benefit from this specific drug is thin, even though the CV-event and safety data are solid.
Side note: my LDL is 36 mg/dL averaged over my last 4 blood draws. I certainly want low LDL to be helpful. And I think it is helpful in a patient population that has heart disease (that is who is being studied here). The question about how helpful it is, on net, in a patient population that does not have heart disease is still an open question in my mind. And most of the people reading this probably fall into the category of primary prevention.
Couldn’t have said it better myself. It is definitely an open question. and IMO the answer is that if you DO NOT already have CVD an ApoB of 60-70 and LDL-c of 60-70 should be good enough, especially if you are also blessed with a somewhat low LPa number. No need to worry too much about lipids and pour all your attention into lowering your hs-CRP and Hb1Ac/FG. Your heart will love you much more than if you tried to lower your already normal lipid numbers LOL. The " hs-CRP and Hb1Ac/FG" should be declared the new “Lipids” for heart health.
I just want to say I disagree quite strongly, assuming that we are measuring LDL at some point long before actual death. In this study that was done.
“In this prespecified analysis, we examined the relationship between achieved LDL-C levels (an average of the first 2 LDL-C levels measured) in FOURIER-OLE (available in 6559 patients) and the incidence of subsequent cardiovascular and safety outcomes.”
“Eligible patients had LDL-C concentrations ≥70 mg/dL or non–high-density lipoprotein cholesterol levels ≥100 mg/dL while on optimized lipid-lowering therapy, including a high- or moderate-intensity statin with or without ezetimibe.”
Well, what about the 75% of all deaths NOT related to CVD? How is it relevant LDL-C in these deaths (s an example, for people that die of cancer, which is a significant#). In other words, by including all deaths you are polluting the data. Or another example unfortunately my cousin fell from third floor (construction) and if his LDL-c was 110 should we blame his death on high LDL-c LOL.
I think that medicine (and all fields, really) suffer from man-with-a-hammer syndrome. We have a tool (hammer) to manage LDL, we use it. When we lack tools to manage other things, we use our hammer.
What I would expect is that within 10 years this will change because we have a new hammer called GLP-1 class drugs, and they have a big impact on A1c and CRP (I think!) as well as Triglycerides, and also on LDL. So we will probably be using this new hammer, and history suggests we will over-focus on what it can treat and neglect something else. Still, it is progress.
Unfortunately, XR was the type I was using. I have tried many methods of using it, but each time it’s like taking a laxative. I have no ideas why my body decided to reject metformin.