#1

I don’t know why this post has been turned into a new thread.

The article sure is not an easy one to understand. Graph 1 is clear enough though, the markers with higher positive correlation with ascertained ASCD (by imaging plaque measurements) are those in cluster 1= DA, AMDA, Log.IL6 mainly. but even the other markers, i cluster 1, exhibit some positive correlation.

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Then there is the pretty clear explanation in the conclusions.

A key finding was that, out of tens of thousands of
blood-based molecules and biomarkers, LDL-TG emerged with
a potential central role in human coronary atherosclerosis,
potentially as a function of abnormal hepatic lipase activity.
This was seen in our hypothesis-free, causal, Bayesian network
analysis, which included 24,929 variables and 110,350 significant
edges in the models. LDL-TG was directly connected to human
coronary atherosclerosis in 95% of the models in the ensemble.

As a comment, the LDL-TG shows a more congruous trend, with small CADs at very small LDL-TG quantities (on y-axes we have ascertained CAD, Cumulative Atherosclerosis Disease, a sort of dose-response relationship)

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#2

Interesting Bayesian machine learning study. Anyway as you said the results are clear, the most important predictor of arteriosclerosis are triglyceride rich ldl particles that are associated with the remnants of vldl.

#3

Does anyone know of any blood test that measure LDL-TG? And any remedies to keep it low?

#4

Figure 2

This suggests that triglyceride-rich lipoprotein particles, as measured by LDL-TG levels, may have a causal role in atherosclerosis. Interestingly, in this causal model, sd-LDL, ApoB, and C-reactive protein are downstream from LDL-TG, while palmitoleic acid and total triglyceride levels appear upstream from LDL-TG.

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#5

One supplement that greatly reduced my triglycerides was Omega-3 fish oil. It had a noticeable benefit.

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#6

The left tails remain interesting in the statin excluded groups. Lower LDL and Apo B but higher CAD incidence. Perhaps confounded by other non-statin cholesterol meds? Or perhaps lower isn’t better?

#7

Cancer is the obvious confounder : Cancer tumors are voracious consumers of cholesterol (as are all cells that divide rapidly, eg wound healing) and will lower LDL cholesterol. However, when statin therapy is added to cancer patients, even with already low LDL, cancer growth slows down, since statin further cuts back on the available plasma cholesterol levels that the cancer can utilize.

The main downside of low cholesterol is impaired speed of wound healing : I suspect humans evolved rising levels of cholesterol with age to deal with the need for rapid wound healing from hunting injuries.

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#8

I always thought plamitoleic acid (macadamia nut oil) was a good thing for insulin sensitivity and other things too. Did this say it’s bad or good?

#9

Slower wound healing or death or impairment by heart attack or stroke. I know which I’d rather choose.

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#10

LDL-TG isn’t related to TG’s per se, it seems more related to apoB.

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#11

Yes, but HDL not LDL.

#12

Finally, Silbernagel et al. (21) demonstrated that LDL-TG was associated with cardiovascular mortality in 3,140 subjects. Genome-wide association study in this cohort demonstrated that variants in the LIPC gene were significantly associated with circulating LDL-TG levels, consistent with our own findings. Furthermore, in a two-sample Mendelian randomization analysis, the authors found that low hepatic lipase activity may be the causal factor behind elevated LDL-TG levels, driving atherosclerotic cardiovascular risk.

The overall data presented here is consistent with our hypothesis that circulating triglyceride-rich LDL particles may have a potential causal role in atherosclerosis due to abnormal hepatic lipase activity.

Stimulants of hepatic HDL production may therefore act through cofactor pathways to stimulate lipolytic enzymes and enhance TG clearance.43 This may in part explain why drugs that increase HDL levels, such as the fibrates and niacin, also reduce plasma TG levels.49,50

The Germans were onto this as early as 2001. See paper below from the University of Marburg.

https://www.ahajournals.org/doi/full/10.1161/hc5001.100795

Low Hepatic Lipase Activity Is a Novel Risk Factor for Coronary Artery Disease

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#13

A similar pattern was also observed for ApoB (Figure 3D). It is acknowledged that the left tails of the cumulative incidence curves are likely to be highly influenced by patients with known ASCAD whose LDL-C and ApoB levels were likely lowered by recent statin therapy. Importantly, statin therapy appears to have little influence on the cumulative incidence of ASCAD as a function of LDL-TG measurements (Figures 3C,F).

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#14

Yes, but the charts posted above specifically say that statin patients are excluded.

#15

The authors’ words not mine.

likely to be highly influenced by patients with known ASCAD whose LDL-C and ApoB levels were likely lowered by recent statin therapy.

I understand that phrase to mean those were patients who already had CVD, and had been given statins. That is standard of care. Recent statin therapy also reinforces my understanding of that statement.