🕺"Exchangeable APOA1 on HDL inhibits LDL binding to proteoglycans"

🏃"HDL inhibition is primarily mediated through APOA1, which directly interacts with LDL to reduce its PG binding

🌈 "Only APOA1 loosely associated with HDL that can transfer to LDL and reduce its PG binding" "The inhibition of LDL-PG binding by HDL is not a new concept. Previous studies have shown that HDL and APOA1 interfere with LDL binding to PGs in various in vitro and in vivo systems"

🌈 "PCSK9 modulates triglyceride-rich lipoprotein (TRL) metabolism, but this impact is modest compared to the impact of PCSK9 on cholesterol metabolism"

💘 "PCSK9 levels are positively associated with plasma TG levels, particularly intermediate-density lipoproteins (IDLs)" "Specific, but not all, PCSK9 gain-of-function and loss-of-function variants impact on TRL metabolism"

"PCSK9 monoclonal antibodies modestly reduce plasma TG levels, mainly by enhancing LDLR-mediated catabolism of IDLs"

Why does this happen in the KETO-CTA study?

Is it inexplicable❓

The claim repeated by many critics about lack of contraste of exposure seems clearly incorrect, but then why❓

The science is not settled..., do the current new data add value to the debate❓

MY THOUGHTS How does hypercholesterolemia occur in these individuals?

See previous post : Keyword ACAT2/Increased Hepatic Secretion/Intestinal overabsorption

https://x.com/lipo_fan/status/1865430031591162214?t=606B6km1V_qtvZM5zO3voA&s=19

🫶"Mechanism of glycocalyx damage during the development of atherosclerosis remains largely unclear"

💚"A heparan analog could relieve atherosclerosis by protecting heparan sulfate from degradation during oxidative stress and by reducing the accumulation of AHSG at lesion sites" "The glycocalyx is the outermost layer of ECs and functions not only as a barrier to protect ECs from damage but also as an interface with vascular tissue and the blood stream for substance exchange and signal transduction."

👀"HYPERCHOLESTEROLEMIA (mostly LDLC) WITHOUT INSULIN RESISTANCE, visceral obesity or other dyslipidemia-related changes

😎Interestingly,NO ATHEROSCLEROTIC PLAQUES developed

😏In vivo evidence fatty streaks do not advance to plaque formation in the absence of insulin resitance" "In summary, the current studies showed that, in the absence of insulin resistance, hypercholesterolemia did not lead to overt atheroma formation or hepatic steatosis despite increased development of inflammation and fibrosis along the aortic wall and in the liver"

"Of greatest importance was that the plasma residence time of sdLDL apo B‐100 (≈74 hours) was much ⬆️ than that observed for lbLDL apo B‐100 (≈40 hours).In our view,sdLDL is substantially more atherogenic than lbLDL because, smaller size and its greater plasma residence time" "When adjustments were made for total cholesterol and cholesterol‐lowering medication in addition to the other risk factors, only sdLDL‐C, direct LDL‐C, LDL‐TG, and lipoprotein(a) remained significant, although the strength of these associations was significantly attenuated"

"LDL-TG was associated with atherosclerosis independently of well-known factors .In Bayesian analysis, LDL-TG was directly linked to atherosclerosis in over 95% of the ensembles. " "Prevalence of atherosclerosis (i.e., cases) was 52% in the overall cohort. 7 % of patients had a coronary calcium score of zero but had a non-calcified plaque. Predominantly non-calcified,partially calcified,calcified plaques were present in 7, 36, & 57% of cases, respectively"

"The present study raises an important
question: are free-living and otherwise healthy individuals with a predominance of small, dense LDL but
without hyperapo-B still at increased CHD risk? " "Although hyperapo-B and small,
dense LDL
commonly coexist in familial combined hyperlipidaemia, it is interesting to note that a significant number
of individuals with this condition and with LDL subclass pattern B have been found with total apo B values well
below 1.3 g/l"

META-ANALYSIS "There was also a strong inverse association between apoA-I quintiles and CR of events in each of the subgroups LDL-C >130, 130-100, 100–70, 70–50,<50 mg/dL. Non-HDL-C was replaced as an ADJUSTMENT variable by either LDL-C or APOB yielded SIMILAR RESULTS". "The strong and inverse association between on-statin HDL-C level and risk of major cardiovascular events was similar in the subgroups of patients achieving on-statin LDL-C >130 mg/dL, 130-100 mg/dL, 100-70 mg/dL, 70-50 mg/dL, and <50 mg/dL"

"In general, subjects with a predominance of large LDL particles have been characterized as having the highest HDL cholesterol levels and lowest triglyceride levels, compared with individuals with smaller LDL particles". "Therefore, it is possible that large LDL particles can be atherogenic but that the risk associated with this trait is usually attenuated or eliminated by virtue of associations with low VLDL and particularly high HDL cholesterol levels in most individuals".

We aimed to evaluate a possible association between Lp(a) levels and clinical outcomes of patients undergoing PCI. Our findings can be summarized as follows: Approximately 30% of PCI patients show an elevated Lp(a) value of more than 50 mg/dL

"Our meta-analysis shows an approximately linear relation between CR and concentrations of Lp(a), which is evident at
Lp(a) 30 mg/dL to less than
50 mg/dL and pronounced at concentrations of 50 mg/dL or higher and persists despite statin treatment". "Lp(a) concentration during follow-up was
associated more strongly with risk for cardiovascular
disease in statins than in those allocated placebo.Comparing individuals with
lipoprotein(a) concentrations of 50 or higher with Lp(a) concentrations lower than
50 mg/dL"

Vegetable Oil or Animal Fat Oil, Which is More Conducive to Cardiovascular Health Among the Elderly in China? "Our study found that cooking with lard/other animal fat oil is more beneficial to cardiovascular health in older Chinese.Dietary guidelines should seriously consider the health effects of substituting vegetable/gingili oil for lard/other animal fat oil for different populations"

"15 mg/dL, 1SD ⬆️ in
genetically predicted HDL-C was associated with a 12% ⬆️ breast cancer risk. Findings were consistent after adjustment for breast cancer RF & were robust in several sensitivity analyses. " Mendelian Randomization "Associations with genetically predicted TG and TC were inconsistent, and no association for genetically predicted LDL-C was observed."