David Diamond Profile picture
Oct 2 15 tweets 9 min read
@JohnKastelein John - Perhaps the only thing we'll agree on is that FH ppl have high LDL and increased CHD early in life (as Mundal et al showed). Where we disagree is why this occurs. As FH ppl have high LDL all their lives, why does CVD mortality decline over time?
@JohnKastelein While the increased CVD mortality early in life is frightening, the magnitude of the mortality overall is small, and all-cause mortality, even early in life, is not statistically significant compared to the non-FH population. So a small % of the FH population dies from CVD.
@JohnKastelein Let's address your comment from 2001 that environmental factors influence FH CHD and mortality.
@JohnKastelein First, LDL-C as well as LDL-P are both composed of heterogeneous components, including sdLDL, which is increased with insulin resistant, and Lp(a), which is an indep CHD risk factor. Thus, high LDL-C or LDL-P, alone, does not address metabolic factors that affect sdLDL vs lbLDL.
@JohnKastelein Indeed, if you look at the population level, high LDL-C is irrelevant when you take into account sdLDL vs lbLDL. The metabolic environment affects which will dominate to become pattern A (healthy) or pattern B (unhealthy) which is assoc with high TG/low HDL.
@JohnKastelein In FH, what is best indicator of CVD risk: coronary calcium (CAC), which is largely indep of LDL. In this study, LDL in statin-treated ppl was equivalent between high and 0 CAC. A major difference: High vs low fasting glucose (indep of LDL).
@JohnKastelein The field has focused on high LDL in FH, but there is a secondary risk factor that is ignored: FH ppl tend to have elevated clotting factors. This is important because environmental/metabolic triggers will produce more CHD in FH by activating clotting factors more readily.
@JohnKastelein What activates clotting factors? Smoking is a strong factor and FH may be more sensitive to the hypercoagulant effect of smoking than non-FH. Look at the vast difference in 25 year CVD free survival between FH smokers and non-smokers.
@JohnKastelein Indeed, smoking was noticed as a survival factor in FH people born in the 19th c and surviving to old age in the 20th
@JohnKastelein In addition, FH ppl are very sensitive to hypertension, which can be ameliorated with #LCHF
Compared hypertensive with non-hypertensive FH 25 year CVD free survival over 25 years.
@JohnKastelein Related to everything in this thread is insulin resistance (e.g., obesity, insulin). As we showed in our review, FH ppl who are not overweight with low insulin have CAD rates equivalent to non-FH taking LDL into account. Again, a risk factor that is ameliorated by #LCHF
@JohnKastelein So, putting this all together, the mechanism common to multiple CVD risk factors, including the subset of FH that develop CVD: hypercoagulation and hypofibrinolysis (not LDL)
@JohnKastelein We covered much this lit in our papers on enhanced coagulation in a subset of FH. This explains ⬆️ CVD, particularly early in life, when activation of clotting factors via metabolism/smoking, takes its toll. This is where survivor bias is specific to clotting, not LDL.
@JohnKastelein As to the small absolute risk benefits of statins, the basis is their pleiotropic, e.g., antithrombotic, effects, which is why statins are more effective in unhealthy (smokers, diabetics) compared to healthy ppl.
@JohnKastelein Finally, you view LDL as inherently atherogenic, I don't.
LDL-p is damaged by the metabolism (⬆️BP, glucose, etc). Native LDL (lbLDL) in a metabolically health person is an energy transport cluster which has been unjustly convicted of causing atherosclerosis.
@bschermd

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More from @LDLSkeptic

Jul 27, 2020
1/18
Thnx @JTMarlin77 @janvyjidak for bringing @nutritiondanny & Alan’s podcast to my attention. The “ripping apart” of my paper is at ~1’15”
sigmanutrition.com/episode343/
Here’s my paper which was discussed:
ebm.bmj.com/content/early/…
2/18
D&A had a lot to say but didn’t actually read my paper. They saw #LCHF advocates in the au list & assumed (incorrectly) the paper advocated #LCHF for FH. They scoffed at my paper, co-written by 5 cardiologists, 2 au with PhDs in nutrition & all authors with an MD and/or PhD
3/18
The giddiness with which D&A discussed the paper was disrespectful, and their ignorance of lipids & FH made them look foolish. They were unprepared to discuss the paper & spent most of their time with ad hom attacks on the authors instead of discussing the science
Read 18 tweets
Nov 22, 2019
Day 2 Statin Adverse Effects:
Please RT to Dayspring & Peter Attia (Both block me)
Increased Brain Amyloid with Statins
dx.doi.org/10.1016/j.dadm…
@FatEmperor @ProfTimNoakes @FructoseNo @DrAseemMalhotra @KenDBerryMD @TuitNutrition
@FatEmperor @ProfTimNoakes @FructoseNo @DrAseemMalhotra @KenDBerryMD @TuitNutrition Day 3 - Statin Adverse Effects:
Dose/Time Dependent Development of T2D
@lowcarbGP @DaveKeto @DavidPerlmutter
@FatEmperor @ProfTimNoakes @FructoseNo @DrAseemMalhotra @KenDBerryMD @TuitNutrition @lowcarbGP @DaveKeto @DavidPerlmutter Day 4: Statin Adverse Effects
Women are more susceptible to develop statin-induced T2D than Men
e100 DIABETES CARE, VOLUME 36, JULY 2013
Read 15 tweets
Jul 27, 2019
Brian, Marion - IMO, you 2 are at extremes and I think of myself somewhere in between.
To Marion - Yes, there are reported harms of statins, no doubt, but if statins were a poison, as you consider it, the adverse effects would be more debilitating and more common.
To Marion, as well, it appears to me that the majority of people have neither benefit nor adverse effects of statins. IMO, the physiology adapts to the statin-induced metabolic intrusion. and functions at a reasonable level.
This of course does not mean I favor statin usage, it means a rigorous assessment of statin adverse effects does not result in massive evidence of harm. The evidence of⬆️T2D is incontrovertible, but may affect only 5% of users, but long-term T2D w/ statins is inknown
Read 7 tweets
Jul 19, 2019
I didn't misrepresent your findings. I quoted your findings that statins didn't reduce sdLDL, which is consistent with other work showing that sdLDL doesn't bind to LDL-r and must be removed by macrophages, which is independent of statin mechanisms. I didn't say you consider
statin effects to be weak - that's my interpretation of how your findings fit with the literature.
You, as well as @kevinnbass , would benefit from seeing the work of @KenSikaris who covers this topic so well:


@DrPaulMason also covers sdLDL beautifully.
When you say statins "work", yes, statins reduce LDL but they do a whole lot more, including reducing inflammation and coagulation. Since the lit is so clear on sdLDL being the atherogenic form of LDL and not large buoyant LDL, it is reasonable to speculate that the pleiotropic
Read 6 tweets
Feb 17, 2019
1) I don't know why I get linked to Koushik's tweets. I shouldn't engage him - he's a nice and sincere person, and has the best of intentions for his patients, but I prefer to connect with scientists and open-minded people, not a priest with daily WFPBD sermons.
2) What Koushik doesn't get is that the source of protein just doesn't matter. People can be healthy as vegetarians, which explains his good health and the good health of his disciples. People can also be healthy consuming meat of any kind, including steak.
3) What really matters? The road to good health contains potholes filled with sugar, or more generally, excess consumption of food that raises blood sugar. Vegetarians, as well as carnivores, can be obese with T2D simply because they consume an excess of high GI foods.
Read 11 tweets
Feb 6, 2019
1) I admire MDs listed here because they recognize benefits of #LCHF diet. They question statin use for primary prevention, but each sees value of statins for 2nd CVD prev. My friendly challenge to them is in this tweet series.
@DrAseemMalhotra @bschermd @DoctorTro @FatEmperor
2) Let's start with the claim that 2nd prev benefits are substantial. The 4S study is often cited, but a 25 year old study with data analyzed by a "Merck employee" has little credibility. There's little after 2004 when standards go tougher; so lets go with the Brit HPS, from 2002
3) The so-called substantial 2nd prev benefits, when one looks at % of ppl w/o an adverse effect in my graph, is small - around 1-3%. The largest effect is the composite of all coronary events, at ~3% better than placebo. Notice that the relative risk is inflated to a 27% ⬇️
Read 13 tweets

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