#102

You don’t have to be trained in statistical analysis to make out that the raw data showed nothing meaningful — that kind of variation is easily attributable to random noise and they needed to continue in order to glean any valid signal. Their halting the experiment under the specious grounds alleged sounds very fishy. Perhaps they expected a very strong signal in favor of the statin and not getting it risked the prospect of ending up with egg on their faces.

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#103

The primary endpoint did show almost a 50% decrease in incidence (0.56 hazard ratio) with a p value that is extremely small, and there was a decrease in secondary endpoints with statistical significance. Any p-value at or below 0.05 is considered significant and not “random noise” as it’s less than 5% chance the result is due to chance.

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#104

The reduction all-cause mortality and reduction in cancer death rates is clearly statistically significant though with a p-value of 0.02 respectively.

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#105

Is there a example of someone with an LDL-C of 40 who got ASCVD?

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#106

Has it been mentioned that the Jupiter trial focussed only on people with high inflammation ? (CRP)

OxLDL % rates vary enormously and can dwarf the ldl and apob rates we’re obsessing over in this forum. The mire U read, the mire convinced i am that reducing inflammation is likely to have a much bigger and more immediate impact than reducing apob below 70. The antiinflammatory affect of statins may have been a big factor in the Jupiter trial tesults.

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#107

Are there MR studies that go this low (apo b 40)?

#108

I like to play with numbers from time to time. As much as I despise statistics. Maybe I will reduce my cognitive decline with age. :innocent: If you want p number for that, I can calculate it.

#109

You can calculate if you want, I would be very surprised if it is significant.

#110

Yes, it is rarely mentioned that OxPLs are an independent casual factor in ASCVD so rarely in this forum.

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#111

Related:

The oxidation of LDL was considered the main atherogenic modification of LDL within the vascular wall for decades. However, recent investigations provided a growing body of evidence in support of the multiple LDL modification theory. It suggests that LDL particles undergo numerous modifications that change their size, density, and chemical properties within the blood flow and vascular wall. Oxidation is the last stage in this cascade resulting in the atherogenic properties. Moreover, recent investigations have discovered that oxLDL may have both anti-inflammatory and pro-inflammatory properties. Oxidized LDL can trigger inflammation through the activation of macrophages and other cells. After all, oxidized LDL is still a promising object for further investigations that have the potential to clarify the unknown parts of the atherogenic process. In this review, we discuss the role of oxLDL in atherosclerosis development on different levels.

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#112

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https://twitter.com/Drlipid/status/1623033709615058976

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#113

Apolipoprotein B-100 (APOB) is a component of fat- and cholesterol-transporting molecules in the bloodstream. It is the main lipoprotein in low-density lipoprotein cholesterol (LDL) and has been implicated in conditions that end healthspan (the interval between birth and onset of chronic disease). However, APOB’s direct relationship with healthspan remains uncertain. With Mendelian randomization, we show that higher levels of APOB and LDL shorten healthspan in humans. Multivariable Mendelian randomization of APOB and LDL on healthspan suggests that the predominant trait accounting for the relationship is APOB. In addition, we provide preliminary evidence that APOB increases risk for Alzheimer’s disease, a condition that ends healthspan. If these relationships are causal, they suggest that interventions to improve healthspan in aging populations could include strategies targeting APOB. Ultimately, given that more than 44 million people currently suffer from Alzheimer’s disease worldwide, such interventions are needed.

Mendelian randomization reveals apolipoprotein B shortens healthspan and possibly increases risk for Alzheimer’s disease, 2024

Ultimately, our findings support the possibility that APOB underlies the causal effects of APOB-containing lipoprotein traits in ending healthspan and increasing the risk for AD. A finer-grained analysis of molecular mechanisms, unfortunately, is beyond our scope but should be part of future research efforts. For now, our results make it considerably more difficult to imagine that maximal strategies for improving healthspan and maintaining optimal cognitive function can ignore APOB.

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#114

Moreover, patients totally deficient for the native LDL receptor are still able to store large amounts of cholesterol in their macrophages. Consequently, they suggested that the classic LDL receptor is not involved in the uptake of modified LDL

From @RapAdmin paper posted above.

So if i measure total LDL mass (via centrifuge) and then use a PCSK9 (or statin) to lower that number, am i removing OxLDL (which promotes ASCVD) as well as LDL (which may not be an issue) to an LDL of say 30, am i depriving myself of some benefit or protection? Or is the risk of ASCVD so great that it dwarfs other risks?

Also, if i take 12mg astraxanthin daily, plus GlyNAC (for glutathione production) daily, does this diminish my risk of LDL being OxLDL and thus my LDL could be higher without the same level of ASCVD risk?

From the quote above: don’t PCSK9 inhibitors reduce “classic” LDL receptors? So we may be managing to a lab value (as the CEO of a mid-sized biotech told me regarding TC) instead of reducing the actual risk?

Asking for a friend….

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#115
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#116

This has been discussed here:

It’s not good

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#117

Every time I see this thread title I just see a big fat

:skull: :skull_and_crossbones:

So I will just mute this thread

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#118

Just one quick aside on the video. Chris Masterjohn mentioned recently ( I forgot where) that his DunedinPACE was .6 something on test 1. I don’t know where you go from there.

#119

I’ve just found this, which is a bit more recent. Looks like they’re inching forwards in this area but i don’t think they’re there yet (in terms of finding oxldl as a better target than apob). It looks like ox-ldl antibodies, if present, modify the risk. So a target may need to include that metric too.

“In addition to oxLDL as a candidate biomarker for CVD, there is a growing body of literature showing the potential role of anti-oxLDL antibodies and other oxLDL-related moieties for CVD risk stratification and promising therapeutic targets”

“The results demonstrated that oxLDL is significantly increased in participants with CVD in the setting of chronic inflammatory conditions. This meta-analysis suggests that oxLDL may be a useful biomarker in risk stratifying cardiovascular disease in chronically inflamed patients.”

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#120

Low LDL-C levels are associated with risk of mortality in a Chinese cohort study

Jie-Ming Lu et al. Endocrine. 2021 Sep.

Abstract

Background and aims: Although low-density lipoprotein cholesterol (LDL-C) has been considered as a risk factor of atherosclerotic cardiovascular disease, limited studies can be available to evaluate the association of LDL-C with risk of mortality in the general population. This study aimed to examine the association of LDL-C level with risk of mortality using a propensity-score weighting method in a Chinese population, based on the health examination data.

Methods: We performed a retrospective cohort study with 65,517 participants aged 40 years or older in Ningbo city, Zhejiang. LDL-C levels were categorized as five groups according to the Chinese dyslipidemia guidelines in adults. To minimize potential biases resulting from a complex array of covariates, we implemented a generalized boosted model to generate propensity-score weights on covariates. Then, we used Cox proportional hazard regression models with all-cause and cause-specific mortality as the dependent variables to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results: During the 439,186.5 person years of follow-up, 2403 deaths occurred. Compared with the median LDL-C group (100-130 mg/dL), subjects with extremely low LDL-C levels (group 1) had a higher risk of deaths from all-cause (HR = 2.53, 95% CI:1.80-3.53), CVD (HR = 1.84, 95% CI: 1.28-2.61), ischemic stroke (HR = 2.29, 95% CI:1.32-3.94), hemorrhagic stroke (HR = 3.49, 95% CI: 1.57-7.85), and cancer (HR = 2.12, 95% CI: 1.04-4.31) while the corresponding HRs in LDL-C group 2 were relatively lower than that in group 1.

Conclusions: Low LDL-C levels were associated with an increased risk of all-cause, CVD, ischemic stroke, hemorrhagic stroke, and cancer mortality in the Chinese population.

PubMed Abstract

Full Text (Paywall)

#121

Low density lipoprotein cholesterol and all-cause mortality rate: findings from a study on Japanese community-dwelling persons

Ryuichi Kawamoto et al. Lipids Health Dis. 2021.

Abstract

Background: Low-density lipoprotein cholesterol (LDL-C) independently impacts aging-related health outcomes and plays a critical role in cardiovascular diseases (CVDs). However, there are limited predictive data on all-cause mortality, especially for the Japanese community population. In this study, it was examined whether LDL-C is related to survival prognosis based on 7 or 10 years of follow-up.

Methods: Participants included 1610 men (63 ± 14 years old) and 2074 women (65 ± 12 years old) who participated in the Nomura cohort study conducted in 2002 (first cohort) and 2014 (second cohort) and who continued throughout the follow-up periods (follow-up rates: 94.8 and 98.0%). Adjusted relative risk estimates were obtained for all-cause mortality using a basic resident register. The data were analyzed by a Cox regression with the time variable defined as the length between the age at the time of recruitment and that at the end of the study (the age of death or censoring), and risk factors including gender, age, body mass index (BMI), presence of diabetes, lipid levels, renal function, serum uric acid levels, blood pressure, and history of smoking, drinking, and CVD.

Results: Of the 3684 participants, 326 (8.8%) were confirmed to be deceased. Of these, 180 were men (11.2% of all men) and 146 were women (7.0% of all women). Lower LDL-C levels, gender (male), older age, BMI under 18.5 kg/m2, and the presence of diabetes were significant predictors for all-cause mortality. Compared with individuals with LDL-C levels of 144 mg/dL or higher, the multivariable-adjusted Hazard ratio (and 95% confidence interval) for all-cause mortality was 2.54 (1.58-4.07) for those with LDL-C levels below 70 mg/dL, 1.71 (1.15-2.54) for those with LDL-C levels between 70 mg/dL and 92 mg/dL, and 1.21 (0.87-1.68) for those with LDL-C levels between 93 mg/dL and 143 mg/dL. This associatioparticularly significant among participants who were male (P for interaction = 0.039) and had CKD (P for interaction = 0.015).

Conclusions: There is an inverse relationship between LDL-C levels and the risk of all-cause mortality, and this association is statistically significant.

From the full text:

"The main finding of this cohort study is that LDL-C is a significant and independent predictor of all-cause mortality in community-dwelling adults. After adjustment for possible confounding factors, the results showed that participants with the very low LDL-C levels (< 70 mg/dL) were at a significantly higher risk for all-cause mortality than those with high LDL-C levels (≥ 144 mg/dL).

Pubmed Abstract

Full Text - Open Access

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