I think it is similar to the hypergrowth concept for mTOR. Our sympathetic nervous system gets turned on too much in modern life, and gets “stuck” in the on position or just gets stronger while the parasympathetic system does not get stronger (unless we are meditating) or gets weaker (if we are not sleeping well). The system gets out of balance, and now we are not good at either responding to threats or recovering from life stress.
Learning to meditate is hard. HRV biofeedback is a nice bridge to learning to meditate effectively, and it might actually do some good in the meantime.
I just finished my interview with Marco Altini PhD of HRV4Training. Stay tuned for the episode. But I’ve already started using HRV biofeedback.
Perhaps oddly, but I am a creature of habit and I take HRV readings twice a day and don’t find that much variation day to day. Fortunately, my readings are consistent with the 25-34 year old age group. I only choose these times because they are convenient for me.
Very good article. Thanks. As opposed to your stable HRV, my HRV is highly variable, during the day as your graph shows, but also between days for readings done at the same time with the same procedures. If I worked out hard, didn’t sleep well, didn’t feel well…my HRV is 50% of my good days.
I get values from Polar and Fitbit. I only record the morning. There is a very obvious affect from alcohol and also a potential effect from the question as to the balance between sympathetic and parasympathetic systems (which can be impacted by melatonin usage).
Going back from today as examples. The larger figure is almost always Polar/Elite.
Lp(a) (Lipoprotein A): Phenotype – Peter recommends knowing Mass and Particle number
APOE Genotype: Risk for Alzheimer’s/greater risk from head injury. People have a mix of 2, 3, and 4 (one from each parent)
Having 2 ApoE4 alleles can increase risk of AD (Alzheimer’s Disease) by 10-20x. Peter argues that this is definitely worth checking as you can in fact prevent Alzheimer’s disease
Things to test at least once a year:
Cardiovascular Health
APOB: APOB is the main protein found in LDL cholesterol. It is the total concentration of LDL and v-LDL which are the big atherogenic particles. Peter thinks a cutoff of less than 90 milligrams per deciliter is good, less than 70, you’re doing great, and less than 50 is pretty optimal and close to perfect. If you want to live to 100, keep it below 30.
Small LDL-P: Peter wants this to be below 500 nmol/L or ~ 25th percentile (20 mg/dl)
Trigs: Most responsive to diet changes (lower carbs); reference is < 150 mg/dL (< 1.7 mmol/L) but Peter wants this < 100 mg/dL (< 1.13 mmol/L); trigs should be lower than HDL.
LDL synthesis: The most preset/not variable
* Better predictive markers than LDL-C (despite C being the more common test)
Keto diet people will have very high levels after a challenge (low before), but this isn’t accurate
Fasting glucose: Only directionally interesting. This varies a lot during the day, difference from 90 or 105 is more about your cortisol level than metabolic issues
Peter uses a Continuous Glucose Monitor (CGM). He doesn’t like the Abbot Freestyle Libre (not accurate enough), has a test version of the Dexcom G6 which is much better. It has a tiny needle, no calibration needed and can connect with your phone
* A month of CGM data is > an OGTT test to Peter
* On CGM, “I like to see my patients with a mean glucose below 100 mg/dL, a glucose variability below 15 mg/dL, and, as noted above, no excursions of glucose above 140 mg/dL.”
DEXA: Look at three things: Appendicular lean mass index (ALMI) and fat-free mass index (FFMI). “I [Peter] aim for my ALMI to be in at least the 90th percentile, if not above the 97th percentile as I age. The data are unequivocal: people live longer, better lives with an ALMI above the 75th percentile.”
He also looks at:
1. Segmental BMD
2. VAT
3. FMI Total
ALT (alanine aminotransferase): Liver health
< 20 U/L and (reference upper limit: 42-44) and AST 40 but Peter wants patients below 20
Best test to see if your liver has issues (side note: ALT elevations are a signal that you should stop taking a new medication – many potential new drugs are stopped if they elevate ALT)
Don’t simply accept it if your Dr. tells you your levels are “normal” as those levels have drifted up over time as the average person has gotten less healthy)
Fatty Liver/NASH will be the leading driver of liver transplant in the future in US
Honorable mentions: Hcy, hs-CRP, fibrinogen, Lp-PLA2, ADMA, SDMA, Estradiol (E2) – these levels keep going up on average in American men; knowing your family history is important.
Family History: More important than doing a whole genome sequence. But behavior matters (e.g. if your grandma smoked and you don’t)
Longevity Markers: Longevity genes include APOE, Lp(a) and then the below:
Heart Disease: The younger you are, the more blood tests can tell you about your risk of cardiovascular disease, older people need to rely more on scans (e.g. CT angiograms)
Omega Index Plus Test: Likes to see EPA/DHA index above 8.5; OmegaQuant offers a good at-home test (use code TROY for 10% off). This is the same test used in Peter’s concierge medical program.
Cancer: Blood gives up the least insight, until liquid biopsy tests become accurate (company like Grail)
Most cancers are somatic mutations not germ line mutations so knowing your genotype doesn’t help much with a few exceptions (e.g. BRCA and Lynch)
As a result, you can focus on inflammation markers and metabolic health
Alzheimer’s Disease: APOE tells you low/medium/high risk and long with risk driven by the same drivers of heart disease, metabolic component, and toxins which we can’t understand/track the least
TOMM40: A TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer’s disease (Roses et al., 2010)
Excellent information! Exactly what I’ve been looking into. I’ll investigate testing for each one and try to decide what meets the standard for being essential and also worth the cost. The total could easily get too expensive. I’ve already added a number of things for my next blood test and picked up some reasonable home testing equipment.
And Biograph… https://en.wikipedia.org/wiki/Fuhgeddaboudit
Yes - everyone is going to have a different cost/benefit tradeoff in terms of which tests and biomarkers are best to track given their medical history, concerns, and budgets.
The functional biomarkers are easier and lower cost… so perhaps relevant to everyone.
@AnUser@L_Hayes this seems to be in the intersection of what you both have argued is important - have you done any blood work like this? Any thoughts on it?
This one does seem like a very important risks factor…?
See review below.
Has anyone done this test?
Oxidized phospholipids in cardiovascular disease | Nature Reviews Cardiology
Abstract
Prolonged or excessive exposure to oxidized phospholipids (OxPLs) generates chronic inflammation. OxPLs are present in atherosclerotic lesions and can be detected in plasma on apolipoprotein B (apoB)-containing lipoproteins. When initially conceptualized, OxPL–apoB measurement in plasma was expected to reflect the concentration of minimally oxidized LDL, but, surprisingly, it correlated more strongly with plasma lipoprotein(a) (Lp(a)) levels. Indeed, experimental and clinical studies show that Lp(a) particles carry the largest fraction of OxPLs among apoB-containing lipoproteins. Plasma OxPL–apoB levels provide diagnostic information on the presence and extent of atherosclerosis and improve the prognostication of peripheral artery disease and first and recurrent myocardial infarction and stroke. The addition of OxPL–apoB measurements to traditional cardiovascular risk factors improves risk reclassification, particularly in patients in intermediate risk categories, for whom improving decision-making is most impactful. Moreover, plasma OxPL–apoB levels predict cardiovascular events with similar or greater accuracy than plasma Lp(a) levels, probably because this measurement reflects both the genetics of elevated Lp(a) levels and the generalized or localized oxidation that modifies apoB-containing lipoproteins and leads to inflammation. Plasma OxPL–apoB levels are reduced by Lp(a)-lowering therapy with antisense oligonucleotides and by lipoprotein apheresis, niacin therapy and bariatric surgery. In this Review, we discuss the role of role OxPLs in the pathophysiology of atherosclerosis and Lp(a) atherogenicity, and the use of OxPL–apoB measurement for improving prognosis, risk reclassification and therapeutic interventions.
Key points
Phosphocholine-containing oxidized phospholipids (OxPLs) induce chronic inflammation, including in atherosclerotic lesions, and can be detected in plasma on apolipoprotein B-100 (apoB-100)-containing lipoproteins.
A method has been developed to quantify OxPLs on a normalized amount of apoB-100 (OxPL–apoB), so that the measurement is independent of plasma apoB-100 and LDL cholesterol levels.
Lipoprotein(a) (Lp(a)) particles carry the largest fraction of OxPLs among apoB-containing lipoproteins; the OxPLs are bound covalently to apolipoprotein(a) and are free in the lipid phase of the associated LDL-like particle.
Plasma OxPL–apoB levels predict the presence and extent of anatomical atherosclerotic cardiovascular disease, and elevated levels are associated with disease in multiple arterial beds; measurement of OxPL–apoB improves prognostication of peripheral artery disease, as well as incident and recurrent myocardial infarction and stroke, and improves risk reclassification, particularly in patients in intermediate risk categories, for whom improving decision-making is most impactful.
Plasma OxPL–apoB levels are reduced by treatment with antisense oligonucleotides aimed at reducing Lp(a) production and by lipoprotein apheresis, niacin therapy and bariatric surgery.
Plasma OxPL–apoB levels predict cardiovascular events with a potency similar to or greater than that of plasma Lp(a) levels, probably because OxPL–apoB levels reflect the levels of the most atherogenic and pro-inflammatory Lp(a) and apoB-100-containing particles.
Yes, I suspect this will be the future of cvd prevention. I haven’t had the test but am looking for a provider in the UK. I’m particularly interested in the impact of the various ldl interventions. My guess would be that statins and then bempedoic acid would have a big benefit impact.
Admittedly not a great take on functional biomarkers, but here it is just because its out there at a popular newspaper, from the Wall Street Journal:
Are You Fit for Your Age? Test Yourself With These Exercises
Measuring your cardiovascular fitness, strength and balance can give a read on how well you’re aging
Having an idea of your so-called fitness age matters. You can slow various declines in health through relatively minor changes, say academics and health professionals. Cardiovascular changes, for example, have been shown to add years to your life.
The first step is to track your fitness benchmarks in areas such as aerobic capacity and muscular endurance. Then, you should aim to keep them in an optimal range to help manage your aging, says Dr. Randall Espinoza, associate director at the UCLA Longevity Center. (You can try some sample tests below.)
Attia has a new company focused on individualized exercise programs for longevity…
This article discusses the approach and some biomarkers they use:
The 10 Squared squad are like fitness precogs in Minority Report, connecting clues in the present to prevent a bad event before it happens in the future. They will triangulate the results from the 30 drills I do for stability, strength, and cardio; factor in my body composition from a DEXA scan; then prescribe a fitness plan to power me for the next five decades. That’s not a typo; this program is not 7-Minute Abs! or Great Shape in 4 Weeks! It’s a training blueprint for your whole life.
The Author’s Key Results & 10 Squared’s Target Numbers
DEXA SCAN: Lean mass (aka muscle)
RESULT: 97th Percentile
GOAL: 75th percentile or above
DEXA SCAN: Body fat
RESULT: 50th percentile
GOAL: 25th percentile (for body fat, lower is better) (I need to go from 23% fat to 18% or lower.)
