较高的低密度脂蛋白胆固醇与较长的寿命有关？

[Virilius]

So study spamming it is then.

Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel | European Heart Journal | Oxford Academic (oup.com)

Reduction in saturated fat intake for cardiovascular disease - Hooper, L - 2020 | Cochrane Library

Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis - PubMed (nih.gov)

There is urgent need to treat atherosclerotic cardiovascular disease risk earlier, more intensively, and with greater precision: A review of current practice and recommendations for improved effectiveness - ScienceDirect

ATV.0000000000000164 (ahajournals.org)

Safety and efficacy of very low LDL-cholesterol intensive lowering: a meta-analysis and meta-regression of randomized trials - PubMed (nih.gov)

Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials - The Lancet

Statins for the primary prevention of cardiovascular disease | Cochrane

Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients | NEJM

[Vlasko]

Low-density lipoprotein cholesterol and all-cause mortality: findings from the China health and retirement longitudinal study.

Liang Zhou et al. BMJ Open. 2020.

Abstract

Objectives: To investigate the relationship between low-density lipoprotein cholesterol (LDL-C) and all-cause mortality among middle-aged and elderly Chinese population.

Design: Prospective cohort study.

Setting: This study used data from the China Health and Retirement Longitudinal Study.

Participants: Middle-aged and elderly participants with complete data were enrolled for a 4-year follow-up of total mortality and plasma levels of LDL-C, including 4981 male respondents and 5529 female respondents.

Results: During a 4-year follow-up, there were 305 and 219 deaths in men and women, respectively. Compared with theZhou L, Wu Y, Yu S, Shen Y, Ke C. Low-density lipoprotein cholesterol and all-cause mortality: findings from the China health and retirement longitudinal study. BMJ Open. 2020 Aug 16;10(8):e036976. doi: 10.1136/bmjopen-2020-036976. PMID: 32801200; PMCID: PMC7430481. first quintile (Q1) of LDL-C, the adjusted HRs (95% CIs) were 0.818 (0.531 to 1.260) for Q2, 0.782 (0.507 to 1.208) for Q3, 0.605 (0.381 to 0.962) for Q4 and 0.803 (0.506 to 1.274) for Q5 in men. The results from restricted cubic spine (RCS) showed that when the 20th percentile of LDL-C levels (84 mg/dL) was used as the reference, a lower LDL-C concentration (<84 mg/dL) was associated with a higher 4-year all-cause mortality risk. By contrast, both quintile analysis and RCS analysis did not show a statistically significant association in women.

Conclusions: Compared with moderately elevated LDL-C (eg, 117-137 mg/dL), a lower plasma level of LDL-C (eg, ≤84 mg/dL) was associated with an increased risk of 4-year all-cause mortality in middle-aged and elderly Chinese men. The results suggest the potential harmful effect of a quite low level of LDL-C on total mortality.

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Zhou L, Wu Y, Yu S, Shen Y, Ke C. Low-density lipoprotein cholesterol and all-cause mortality: findings from the China health and retirement longitudinal study. BMJ Open. 2020 Aug 16;10(8):e036976. doi: 10.1136/bmjopen-2020-036976. PMID: 32801200; PMCID: PMC7430481.
Full Text

[AnUser]

I think this bot is malfunctioning.

[Virilius]

Relations of Change in Plasma Levels of LDL‐C, Non‐HDL‐C and apoB With Risk Reduction From Statin Therapy: A Meta‐Analysis of Randomized Trials | Journal of the American Heart Association (ahajournals.org)

Europe PMC

9789241565349-eng.pdf (who.int)

Long-term secondary prevention of cardiovascular disease with a Mediterranean diet and a low-fat diet (CORDIOPREV): a randomised controlled trial - PubMed (nih.gov)

Effect of cutting down on the saturated fat we eat on our risk of heart disease | Cochrane

Dietary intake of total, animal, and plant proteins and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of prospective cohort studies - PMC (nih.gov)

[Virilius]

When Russians send their spammers they are not sending their best.

[Vlasko]

@RapAdmin

Sure, there is discussion of how low is optimal, but thats a different issue than these papers are suggesting.

I think it goes without saying that the prevailing wisdom or common belief is that LDL-C should be kept in a certain range or at least below a certain threshold to reduce the risk of adverse health outcomes. However, there really isn’t a scientific consensus, either, which may come as a surprise to most people. More like a prevailing majority stance. My intent here was to show that there is a significant number of researchers with statistical findings that contradict mainstream thought and call into question the current criteria used to determine when initiation of cholesterol-lowering therapy may be prudent. And this includes articles and studies in the BMJ. If nothing else, these studies (and more that I haven’t included here) raise concerns over the current reference ranges that are relied on by physicians to make decisions on pharmacological intervention.

[Virilius]

We have direct evidence from intervention trials which trump any and all observational trials that lowering LDL-C lowers mortality.
Why do you ignore the pyramide of evidence? Why do you keep citing fringe papers? This just screams agenda.

[AnUser]

@Vlasko

However, there really isn’t a scientific consensus, either, which may come as a surprise to most people.

@Vlasko

that contradict mainstream thought

So there isn’t a scientific consensus, but there is mainstream thought? Even though you seem to contradict yourself, I can assure you outside of CIS, there is a medical consensus on the matter. Just look up ACC guidelines for America or ESC in Europe. With over 50,000 cardiology members for the former and 100,000 for the latter. But it doesn’t matter since your papers have been debunked by the other posts in this thread.

[Ericross2]

I’m not arguing any of the points here, and I’m actively seeking ways to lower my LDL to lower my overall ASCVD risk. But i might suggest that, as ASCVD mortalities seem to be increasing even in light of “consensus” by cardiologists, perhaps we should at least consider approaches to the strategies that seem to be trending ASCVD in the wrong direction?

(Grenade thrown….)

[Ericross2]

Many of these studies are in the elderly: perhaps there isn’t enough time for the damage of higher LDL over decades to play out, and that’s why we dont see a relationship here?

[Virilius]

@Ericross2

But i might suggest that, as ASCVD mortalities seem to be increasing even in light of “consensus” by cardiologists

Only globally. In the West, ASCVD mortality rates have strongly decreased in the past decades.

[AnUser]

No RapAdmin has already posted about this in another thread with graphs where it has been trending down over the decades. It peaked in the 1950’s.

The worst this information will do is make people not target apoB even lower. People are not fooled by this anymore to ignore lipids totally. And the doctors who have been in the business for long don’t see people flood into hospitals with cardiovascular disease anymore.

@Ericross2

Many of these studies are in the elderly: perhaps there isn’t enough time for the damage of higher LDL over decades to play out, and that’s why we dont see a relationship here?

You don’t see a relationship because of reverse causation. Cancer, parasitic infections, liver disease, frailty, anorexia, all decrease LDL, for example. Those that die from the diseases that lower LDL, it makes the data noisy and you don’t know whether decreasing LDL is causing this or the diseases. I spelled this out for @Vlasko

If 50% of Elders with low LDL died because they ate very little food, that does not mean it is the low LDL that is causing the problem. Or if they had parasitic infections, or cancer…

Association studies can impossibly control for all of these confounding factors even though they try sometimes.

That’s why you use studies done with mendelian randomization, where you look at genes that only increase or decrease LDL. Because they are randomly assigned at birth and do not do anything else, and have their effect not dependent on what a person does, you can find the effect without reverse causation. And not surprisingly those with low LDL live longer, have less cardiovascular disease, etc, and the relationship matches the randomized controlled trials which is the other study design that can control for these confounding factors. The relationship between disease and LDL levels is perfectly the same between both study designs. So the short answer is all of these studies posted by Vlasko have negative utility and anyone who takes them seriously and follows the advice will probably get atherosclerosis, erectile dysfunction, then a heart attack.

[Vlasko]

The study below suggests there may be an association between low LDL-C and CKD. “LDL-C concentration below 3.5 mmol/L may increase the risk of CKD.” That’s equivalent to 63 mg/dl. And NIH guidelines have a preferred LDL range of 50 - 70 mg/dl.

Investigating linear and nonlinear associations of LDL cholesterol with incident chronic kidney disease, atherosclerotic cardiovascular disease and all-cause mortality: A prospective and Mendelian randomization study

Zhenqian Wang et al. Atherosclerosis. 2023 Dec.

Background and aims: Observational studies suggest potential nonlinear associations of low-density lipoprotein cholesterol (LDL-C) with cardio-renal diseases and mortality, but the causal nature of these associations is unclear. We aimed to determine the shape of causal relationships of LDL-C with incident chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality, and to evaluate the absolute risk of adverse outcomes contributed by LDL-C itself.

Methods: Observational analysis and one-sample Mendelian randomization (MR) with linear and nonlinear assumptions were performed using the UK Biobank of >0.3 million participants with no reported prescription of lipid-lowering drugs. Two-sample MR on summary-level data from the Global Lipid Genetics Consortium (N = 296,680) and the CKDGen (N = 625,219) was employed to replicate the relationship for kidney traits. The 10-year probabilities of the outcomes was estimated by integrating the MR and Cox models.

Results: Observationally, participants with low LDL-C were significantly associated with a decreased risk of ASCVD, but an increased risk of CKD and all-cause mortality. Univariable MR showed an inverse total effect of LDL-C on incident CKD (HR [95% CI]:0.84 [0.73-0.96]; p = 0.011), a positive effect on ASCVD (1.41 [1.29-1.53]; p<0.001), and no significant causal effect on all-cause mortality. Multivariable MR, controlling for high-density lipoprotein cholesterol (HDL-C) and triglycerides, identified a positive direct effect on ASCVD (1.32 [1.18-1.47]; p<0.001), but not on CKD and all-cause mortality. These results indicated that genetically predicted low LDL-C had an inverse indirect effect on CKD mediated by HDL-C and triglycerides, which was validated by a two-sample MR analysis using summary-level data from the Global Lipid Genetics Consortium (N = 296,680) and the CKDGen consortium (N = 625,219). Suggestive evidence of a nonlinear causal association between LDL-C and CKD was found. The 10-year probability curve showed that LDL-C concentrations below 3.5 mmol/L were associated with an increased risk of CKD.

Conclusions: In the general population, lower LDL-C was causally associated with lower risk of ASCVD, but appeared to have a trade-off for an increased risk of CKD, with not much effect on all-cause mortality. LDL-C concentration below 3.5 mmol/L may increase the risk of CKD.

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Wang Z, Xiao Y, Lu J, Zou C, Huang W, Zhang J, Liu S, Han L, Jiao F, Tian D, Jiang Y, Du X, Ma RCW, Jiang G. Investigating linear and nonlinear associations of LDL cholesterol with incident chronic kidney disease, atherosclerotic cardiovascular disease and all-cause mortality: A prospective and Mendelian randomization study. Atherosclerosis. 2023 Dec;387:117394. doi: 10.1016/j.atherosclerosis.2023.117394. Epub 2023 Nov 19. PMID: 38029611.
Abstract

[AnUser]

That is much better, thank you for not posting those association studies anymore. I will have a look at this.

[AnUser]

I don’t have access to the full paper but it says it was mediated by HDL and triglycerides:

These results indicated that genetically predicted low LDL-C had an inverse indirect effect on CKD mediated by HDL-C and triglycerides

[Vlasko]

Below is one of the most important recent studies. It was published in the Journal of the American Heart Association (JAHA). Concisely stated, researchers investigated the, “Association of Low‐Density Lipoprotein Cholesterol Levels with More than 20‐Year Risk of Cardiovascular and All‐Cause Mortality in the General Population.” They found that, “Both very low and very high LDL‐C levels were associated with increased risks of CVD mortality. Very low LDL‐C levels was also associated with the high risks of all‐cause and stroke mortality.”

So what is very low LDL-C? They have that as LDL‐C below 70 mg/dL. From the full text:

“In a nationally representative cohort with a median follow‐up of 23.2 years, we found very low LDL‐C levels <70 mg/dL was associated with increased risks of all‐cause, CVD and stroke mortality. Moreover, very high LDL‐C levels ≥190 mg/dL were also associated with increased CVD and CHD mortality. […] The results also showed that LDL‐C level was not associated with risk of cancer mortality.”

But as noted earlier, the NIH currently recommends a target LDL of 50 - 70 mg/dl: “The target level of LDL-C is between 50 to 70mg/dl to prevent plaque formation in the blood vessels.”

And for pharmacological intervention, they say, “Start moderate-intensity statin therapy […] in those non-diabetic patients with a level of LDL-C greater than or equal to 70 mg/dL and a 10-year ASCVD risk more than 7.5%.”

Source

Association of Low-Density Lipoprotein Cholesterol Levels with More than 20-Year Risk of Cardiovascular and All-Cause Mortality in the General Population

Shuang Rong et al. J Am Heart Assoc. 2022.

Abstract

Background Current cholesterol guidelines have recommended very low low-density lipoprotein cholesterol (LDL-C) treatment targets for people at high risk of cardiovascular disease (CVD). However, recent observational studies indicated that very low LDL-C levels may be associated with increased mortality and other adverse outcomes. The association between LDL-C levels and long-term risk of overall and cardiovascular mortality among the U.S. general population remains to be determined. Methods and Results This prospective cohort study included a nationally representative sample of 14 035 adults aged 18 years or older, who participated in the National Health and Nutrition Examination Survey III 1988-1994. LDL-C levels were divided into 6 categories: <70, 70-99.9, 100-129.9, 130-159.9, 160-189.9 and ≥190 mg/dL. Deaths and underlying causes of deaths were ascertained by linkage to death records through December 31, 2015. Weighted Cox proportional hazards regression models were used to estimate the hazard ratios (HR) of mortality outcomes and its 95% CIs. During 304 025 person-years of follow up (median follow-up 23.2 years), 4458 deaths occurred including 1243 deaths from CVD. At baseline, mean age was 41.5 years and 51.9% were women. Very low and very high levels of LDL-C were associated with increased mortality. After adjustment for age, sex, race and ethnicity, education, socioeconomic status, lifestyle factors, C-reactive protein, body mass index, and other cardiovascular risk factors, individuals with LDL-C<70 mg/dL, compared to those with LDL-C 100-129.9 mg/dL, had HRs of 1.45 (95% CI, 1.10-1.93) for all-cause mortality, 1.60 (95% CI, 1.01-2.54) for CVD mortality, and 4.04 (95% CI, 1.83-8.89) for stroke-specific mortality, but no increased risk of coronary heart disease mortality. Compared with those with LDL-C 100-129.9 mg/dL, individuals with LDL-C≥190 mg/dL had HRs of 1.49 (95% CI, 1.09-2.02) for CVD mortality, and 1.63 (95% CI, 1.12-2.39) for coronary heart disease mortality, but no increased risk of stroke mortality. Conclusions Both very low and very high LDL-C levels were associated with increased risks of CVD mortality. Very low LDL-C levels was also associated with the high risks of all-cause and stroke mortality. Further investigation is needed to elucidate the optimal range of LDL-C levels for CVD health in the general population.

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Rong S, Li B, Chen L, Sun Y, Du Y, Liu B, Robinson JG, Bao W. Association of Low-Density Lipoprotein Cholesterol Levels with More than 20-Year Risk of Cardiovascular and All-Cause Mortality in the General Population. J Am Heart Assoc. 2022 Aug 2;11(15):e023690. doi: 10.1161/JAHA.121.023690. Epub 2022 Jul 29. PMID: 35904192; PMCID: PMC9375485.
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[Virilius]

Also only a cohort study.

[JuanDaw]

https://vernerwheelock.com/179-cholesterol-and-all-cause-mortality/

Cites studies from
Japan, Norway, The Netherlands, Hawaii, Austria, Finland.

Conclusion

Without exception all-cause mortality is highest in those with the lowest levels of TC. In older people those with the highest cholesterol have the highest survival rates, irrespective of where they live in the world. The picture which emerges is totally consistent. The research which triggered the concern about heart disease was based almost entirely on middle-aged men and was restricted to heart disease. *

But what is so striking about all the studies cited here is that when the focus is on older people, which is when the vast majority deaths occur, and on all-cause mortality the perception of the risks associated with cholesterol are reversed.*

It is also highly significant that these results do NOT conflict with the research on middle-aged men and heart disease. The data from Honolulu confirm that in those involved in the study with low cholesterol there was a low death rate from heart disease but crucially the incidence of cancer was relatively high and demonstrates why it is vital to consider the big picture.

The emphasis on TC and LDL cholesterol as risk factors was based on a complete failure to do so. There is absolutely no logical justification for advising people to lower their TC or their LDL cholesterol. On the contrary all the evidence which is now available indicates that that the higher the better. The results for women are quite exceptional and show consistently that those with the highest TC values invariably have the greatest life expectancy.

About the writer

I was brought up in Co. Wexford and had most of my education in Belfast finishing off with degrees in Chemistry and Agricultural Chemistry from Queen’s University. I spent 5 years at the National Institute for Research in Dairying and was awarded a PhD b from the University of Reading. This was followed by a period at the University of Bradford, where I established the Food Policy Research Unit. The main focus of the Unit was to conduct research various issues related to the production and consumption of food. In 1990 I started a business Verner Wheelock Associates, which provides HACCP training and consultancy for food companies.

https://vernerwheelock.com/about/

[Vlasko]

Another recent review below. And as noted by the researchers at the start of their abstract, “The association between low density lipoprotein cholesterol (LDL-C) and all-cause mortality has been examined in many studies. However, inconsistent results and limitations still exist.”

They looked at the “Nutrition Examination Survey (NHANES) data with 19,034 people to assess the association between LDL-C level and all-cause mortality.” They found that, “low level of LDL-C is associated with higher risk of all-cause mortality.”

Per the full text, they write,

"To the best of our knowledge, this is the first study to find a significant relationship between low LDL-C level and all-cause mortality in population with a broad age range using a nationally representative sample of US (NHANES 1999–2014). The NHANES data provided us with a unique opportunity to study the association between LDL-C level and all-cause mortality in a large multiethnic, nationally representative sample of the US population. In addition, we were also able to adjust for a wide range of potential confounders such as sociodemographic characteristics and health-related disease factors to assess the true association between LDL-C level and all-cause mortality in the general population.

“In a nationally representative sample of US, low LDL-C level [< 70 mg/dl] was found to be associated with higher risk of all-cause mortality after adjusting for confounding factors, such as age, sex, race, marital status, education level, smoking status, BMI, hypertension, diabetes, cardiovascular disease, cancer.”

And as previously noted, the NIH currently recommends a target LDL of 50 - 70 mg/dl: “The target level of LDL-C is between 50 to 70mg/dl to prevent plaque formation in the blood vessels.”

Association between low density lipoprotein cholesterol and all-cause mortality: results from the NHANES 1999-2014

Ya Liu et al. Sci Rep. 2021

Abstract

The association between low density lipoprotein cholesterol (LDL-C) and all-cause mortality has been examined in many studies. However, inconsistent results and limitations still exist. We used the 1999-2014 National Health and Nutrition Examination Survey (NHANES) data with 19,034 people to assess the association between LDL-C level and all-cause mortality. All participants were followed up until 2015 except those younger than 18 years old, after excluding those who died within three years of follow-up, a total of 1619 deaths among 19,034 people were included in the analysis. In the age-adjusted model (model 1), it was found that the lowest LDL-C group had a higher risk of all-cause mortality (HR 1.708 [1.432-2.037]) than LDL-C 100-129 mg/dL as a reference group. The crude-adjusted model (model 2) suggests that people with the lowest level of LDL-C had 1.600 (95% CI [1.325-1.932]) times the odds compared with the reference group, after adjusting for age, sex, race, marital status, education level, smoking status, body mass index (BMI). In the fully-adjusted model (model 3), people with the lowest level of LDL-C had 1.373 (95% CI [1.130-1.668]) times the odds compared with the reference group, after additionally adjusting for hypertension, diabetes, cardiovascular disease, cancer based on model 2. The results from restricted cubic spine (RCS) curve showed that when the LDL-C concentration (130 mg/dL) was used as the reference, there is a U-shaped relationship between LDL-C level and all-cause mortality. In conclusion, we found that low level of LDL-C is associated with higher risk of all-cause mortality. The observed association persisted after adjusting for potential confounders. Further studies are warranted to determine the causal relationship between LDL-C level and all-cause mortality.

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Liu Y, Liu F, Zhang L, Li J, Kang W, Cao M, Song F, Song F. Association between low density lipoprotein cholesterol and all-cause mortality: results from the NHANES 1999-2014. Sci Rep. 2021 Nov 11;11(1):22111. doi: 10.1038/s41598-021-01738-w. PMID: 34764414; PMCID: PMC8586008.
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[Virilius]

You keep posting the same kinds of observational studies while ignoring obvious explanations like stated by @JuanDaw and myself in that cancer can explain this discrepancy. Intervention trials consistedly paint the same picture: the higher the LDL-C the higher mortality. Lowering LDL-C via statins or lifestyle also lowers plaque volume The effects of lipid-lowering therapy on coronary plaque regression: a systematic review and meta-analysis | Scientific Reports (nature.com).

Are yout trying to convince yourself that high cholsterol isn’t damaging your body or do you believe that by spamming cohort studies (I have posted more actual studies btw) you will somehow convince the readers on here of your fringe hypothesis?

Here is a picture of the hierarchy of evidence in case you forgot.