1/19 1/x Let’s start with the basics- what are the different types of fats: saturated, monounsaturated and polyunsaturated. These are defined by the # of carbon-carbon double bonds of the fatty acids that are amenable to reactions.
2/19 In terms of effects on LDL-C, excessive intake of saturated fats raises LDL-C and mono and poly are neutral or lower LDL-C. This has to do mainly with how the fats interact with genes in the liver to affect LDL metabolism.
3/19 On other hand, the opposite occurs with oxidation: sat fats cannot be oxidized, mono are difficult to oxidize, and poly are very easy to oxidize. For a simple and superficial explanation, oxidation is the addition of oxygen to the fatty acid at the site of the double bonds,
4/19 which are derived from oxygen free radicals, creating complex structures called oxidation-specific epitopes (OSE) - term was coined in our lab by Joe Witztum. OSE are highly pro-inflammatory and active the innate immune system to create inflammation-a topic for another time
5/19 LDL is composed of: saturated fatty acids (~35%), mono (~25%), and poly (~45%), which is mainly linoleic acid. Small amounts of omega 3s are also present. ncbi.nlm.nih.gov/pubmed/9888874
6/19 In a study in 1998, we showed that if LDL has high oleic acids content from olive oil, the LDL is difficult to oxidize and it also is associated with less monocyte chemotaxis and adhesion, despite similar plasma LDL-C levels, a beneficial effect in early atherosclerosis.
7/19 OK, so how is this related to Lp(a)? Lp(a) has an apoB particle in it that is very similar if not identical to LDL.
8/19 Dietary studies are difficult to interpret because when you add one thing, you need to take something else away if you keep calories constant, so there are always at least 2 variables changing, so cause and effect are difficult to ascribe.
9/19 Nonetheless, these are the key take home message in dietary studies and Lp(a):
1.Dietary studies show heterogenous results and no consistent results are shown, but the weight of the evidence is that small effects (up to +/- 20%) can be seen in various studies.
1/13 Today, we have a special guest, @MWilkinsonMD presenting: "Saturday Morning Class #25- Lp(a) and plant based diet" Thank you Mike, and enjoy..
2/13 1. Thanks @LPadoc for the invitation to discuss diet and Lp(a)!
3/13 2. First, it is important to distinguish studies of macronutrients vs diet styles. There is clear evidence that plant-based diet styles can reduce CV risk, e.g. Med Diet, DASH link.springer.com/book/10.1007/9…
See chapter on Plant-Based Diets
1-Lp(a) HERITAGE, in US cohort, 25% had Lp(a)>70 mg/dL in overall cohort and 40% in Black participants, otherwise eligible for the trial @Novartis
2-Intermountain Health data (mostly white), 17% had Lp(a)>70 mg/dl, and had higher MACE
3/9
3-Mass General cohort: elevated Lp(a) a risk factor in both men and women
4-Olpasiran lowers Lp(a) equally irrespective of baseline Lp(a). Known for pelacarsen. All well-designed RNA therapeutics should have this property.
1/9 Summary of ESC 2022 highlights: @escardio
Lp(a) topics- 5 sessions, 2 industry sessions, ~25 abstracts:
1- Big news was @society_eas consensus statement (not guideline). Nice overview of the field in last 10 years. Bottom line, measure Lp(a) in all adults once.
2/9 Its similar to 2019 ESC/EAS guidelines, but did not qualify it to measure to pick up very high risk pts, so less likely to be criticized by payors 2- Risk of Lp(a) fairly continuous 3- Several other topics covered-very comprehensive.
3/9 4- Treat according to overall risk, and manage other risk factors optimally. 5- No other groundbreaking statements, wait for CVOT data
With apoB getting more press, its time for some Twitter balance. My take is I rarely use it, as i need to know individual components, LDLC, Lp(a) and TG for Rx. So, here are 4 polls to set discussion: #1: I find measuring apoB changes my Rx decision x% of time
#2 which drugs “directly” lower apoB as their primary mechanism?
#3 The following conditions are associated with hepatic steatosis/⬆️ LFTs when apoB metabolism is severely disturbed;
1/4 Q#3 f/u: OK folks, this is the result of his genetic tests via @GBHealthWatch:
It shows he is heterozygous for a pathogenic ABCG5 mutation, c/w sitosterolemia. Not homozygous. No other FH/LDL mutations noted.