心血管健康

[RapAdmin]

[AnUser]

Thomas Dayspring is not an Immortalist / Don’t Die enthusiast or at least what I know, almost like Peter Attia. He is a lipidologist. If you have different goals you need a different approach I think or at least combine it. Lower in that case, of course.

[LukeMV]

I watched this entire video when it first came out and I have to say, it is probably the most comprehensive instructional video of exercise for longevity on the internet. Strongly recommend for anyone, even those of us who think we already knew a lot about exercise.

[Jerry_Cahill]

I have read quite a bit on this as well as watched some Youtube videos. Currently I think Dr. Ford Brewer has some of the most basic straight forward videos on this topic.

[adssx]

He recommends apoB < 70 mg/dL in most people and apoB < 50 mg/dL in “high-risk” people.

But his definition of “high-risk” is very broad and, I’m sure, includes at least a third of the population (high Lp(a), TG, HbA1c, insulin, homocysteine, hs-CRP, etc.):

[adssx]

Association of Plasma Omega-3 Levels With Incident Heart Failure and Related Mortalities 2024

In participants without HF at baseline (n=271,794), a generally linear inverse association was observed between omega-3 levels and incident HF during a median follow-up of 13.7 years. The risk was 21% lower in the highest quintile of omega-3 compared with the lowest quintile (hazard ratio, 0.79; 95% CI, 0.74 to 0.84; P<.001) in multivariable models.
In parallel models in participants with prevalent HF (n=1239), risk for all-cause and CV mortality were both reduced by approximately 50% comparing top to bottom omega-3 quintiles (hazard ratio, 0.53; 95% CI, 0.33 to 0.86; and hazard ratio, 0.50; 95% CI, 0.31 to 0.79, respectively; both P<.01).

The two interesting charts:

Figure 1. Forest plot illustrating the association between omega-3 plasma levels and the incidence of heart failure (HF). As omega-3 plasma levels increase, there is a concurrent decrease in the risk (ie, lower hazard ratio [HR]) of HF. Hazard ratios associated with docosahexaenoic acid (DHA) are shown in light gray, with total omega-3 in light green and non-DHA in dark green. Adjusted for age, sex, race/ethnicity, history of coronary heart disease, low-density lipoprotein to high-density lipoprotein cholesterol ratio, cholesterol medication, hypertension, diabetes mellitus, smoking status, alcohol consumption, level of education, exercise, body mass index, and waist circumference. Q, quintile.

Figure 2. Forest plots depicting the relationship between omega-3 plasma levels and all-cause mortality (A) and cardiovascular mortality (B). As omega-3 plasma levels increase, there is a corresponding decrease in the risk of all-cause mortality (A) and cardiovascular mortality (B). Hazard ratios associated with DHA are shown in light gray, with total omega-3 in dark green, and non-DHA in black. Adjusted for age, sex, race/ethnicity, history of coronary heart disease, low-density lipoprotein to high-density lipoprotein cholesterol ratio, cholesterol medication, hypertension, diabetes mellitus, smoking status, alcohol consumption, level of education, exercise, body mass index, and waist circumference. Q, quintile.

So to be in the top quintile, you need:

• Serum DHA: >2.47%
• Serum total omega 3: >5.45% ( This is NOT the omega 3 index as the omega 3 index looks at RBC and not serum )
• Serum non-DHA: >3.13%

Regarding non-DHA, they note:

In our study, when comparing the plasma levels of DHA, non-DHA, and total omega-3 as exposure markers, associations with risk for HF were somewhat stronger for non-DHA than DHA. For the mortality outcomes, differences in HRs were reasonably similar with all 3 metrics. An interlaboratory experiment (see Patients and Methods) confirmed that the strongest predictor of non-DHA omega-3 levels was EPA (R2=46.8%), while neither alpha-linolenic acid nor docosapentaenoic acid were statistically significant predictors (P>.05 in both cases) of the non-DHA omega-3 level. Thus, it appears (although only inferred) that a higher EPA level may have been more directly linked to the lower incidence of HF than a higher DHA level. This finding aligns with the results from the Multi-Ethnic Study of Atherosclerosis (MESA), which reported that higher plasma EPA levels were significantly associated with reduced risk for HF after 13 years of follow-up.

[AnUser]

@adssx

He recommends apoB < 70 mg/dL in most people and apoB < 50 mg in “high-risk” people.

Context matters, if you asked him that you wanted to try to avoid atherosclerotic disease forever he would probably say to target 30 mg/dl or lower.

There are barely any side effects of ezetimibe and PCSK9 inhibitor.

That must mean these are true longevity drugs. And obicetrapib might join that camp soon as well.

[adssx]

@AnUser

Context matters, if you asked him that you wanted to try to avoid atherosclerotic disease forever he would probably say to target 30 mg/dl or lower.

Not sure:

[Dexter_Scott]

All exercise is not the same. If 4-5 days of exercise per week is optimal, what does that mean? Does he quantify the hours per day or type(s) of exercise one should do? Cardio, lifting, walking, Tai Chi, what?

[RapMet]

Well, there wasn’t that long ago we discussed various exercise studies which found that even light exercise provides 95% of the benefits of intense exercise. so, don’t know what to make of it. I guess these studies tend to change based on weather outside lol.

[John_Hemming]

What I think is clear is that there is perhaps a minimum of 7,000 steps a day that provides useful exercise after that point there remain marginal improvements until people go into the endurance type of exercise.

[adssx]

@adssx

Association of Plasma Omega-3 Levels With Incident Heart Failure and Related Mortalities 2024

By the same author: Omega-3 fatty acids in primary and secondary prevention of cardiovascular diseases 2024

The optimal levels of Ω-3 index appear to be 8% or greater,36 which has generally been accepted as the standard target for this risk factor. Furthermore, based on data evaluated in 2023 of a meta-analysis including 58 studies, practical recommendations to improve Ω-3 index to ≥8% are consumption of 1000–1500 mg/d EPA/DHA for at least 12 weeks. The inconsistent results of prior Ω-3 studies were likely heavily influenced by the complexity of Ω-3 bioavailability and dosing issues, but also may be related to the specific CVD outcome being studied. As discussed previously, there is data suggesting a more linear relationship between dosing and benefit with nonfatal CHD events and a plateau effect when analyzing dosing benefits involving CVD mortality.
One important question is whether EPA, DHA, or some combination of both is more effective in preventing CVD outcomes. There is the belief that EPA is better for CVD prevention given observations that DHA supplementation can increase LDL-cholesterol levels. One study found high-dose DHA increases LDL turnover and contributes to larger LDL particles compared with EPA; however, large LDL particles are linked to lower risk of CVD as compared to small LDL particles.
Regardless, there is a more significant amount of data involving the benefits of Ω-3 PUFAs and atherosclerotic plaque stability with EPA versus EPA + DHA.
Furthermore, a meta-analysis conducted by Jia et al., which included data from over 83,000 patients, found a 51% increased risk of AF with higher doses of Ω-3 (>1 g daily) and a much smaller increased risk (12%) associated with lower doses (≤ 1 g daily). In light of these findings, it may be advisable to consider shared decision-making regarding AF risk for individuals at high risk. However, for most patients, the cumulative cardiovascular benefits of low-dose Ω-3 likely outweigh the associated risks.
Conclusions: A robust and significant proportion of data supports the efficacy of Ω-3 at therapeutic levels in both the primary and secondary prevention of CVD. It appears the primary unanswered questions relate to the optimal mix of EPA and DHA and ideal target doses of these Ω-3 fatty acids. Research employing higher doses of Ω-3 typically results in more uniform CVD benefits, though these outcomes may vary according to the specific CVD endpoints assessed. The Ω-3 index has been proposed as a tool to navigate these dosage concerns, yet it has not gained widespread traction in clinical settings. It is evident an information gap exists on this topic, and RCTs utilizing the Ω-3 index could provide clarity. The AHA recommendations seem to align with current evidence, endorsing Ω-3 supplementation for individuals at elevated risk or established CVD and for those with elevated TG levels. Despite advancements in CVD treatment modalities, the medical community should consider the use of Ω-3 supplementation, especially when accounting for the solid empirical support it has demonstrated, rather than rejecting it based on neutral results from suboptimal trials that do not fully account for its complex bioavailability.

My conclusion based on the available evidence (and what I started last month):

• Measure omega 3 index
• If close to 8%: focus on diet
• If far below 8%, see how much you need to supplement: Omega-3 Index Calculator | OmegaQuant
• Supplement in EPA only accordingly. If at risk of AF, then limit the dose to 1 g/day.
• Remeasure 4 months later and adjust if needed.

[AnUser]

The boss has a more recent post of this:

I think he’s correct that there would be not much of any side effects.

Genetic causes might for example have an altered APOB gene causing malformed and malfunctioning apoB48 and apoB100, where the former is transporting lipids from the intestines. So if I would guess it kind of implies a level of precisely 0 apoB since it does not function, including apoB48. It would be interesting to look more in detail at PCKS9, NPC1L1, or CETP loss of function instead and related to fatty liver disease and fat soluble vitamins.

If you knock out PCKS9 you’re increasing LDL receptors on the liver making it take up more apoB’s, instead of affecting synthesis and transport of apoB48 from the intestines, for example. ApoB48 has a chance to deliver the energy and phospholipids to the muscles before the LDL receptors take them in at <30 mg/dl apoB. But he seems happy about 30 mg/dl apoB without any of these side effects.

It also probably depends on diet and other lifestyle factors if so. If it’s high in saturated fat that might cause fatty liver more (increase in serum LDL from it might be downregulation of LDL receptors to protect the liver).

So I’m targeting 30 mg/dl apoB to halt or prevent the progression of atherosclerosis and all of the negative events (stroke, heart attack, exercise intolerance, heart pain, etc), maybe even lower later. If there was any reason to believe it would increase fatty liver or vitamin deficiencies at lower levels, that I assume can be easily monitored.

[LukeMV]

Good new video here

The 4 Horsemen Of Death, Starting TRT, Longevity Drugs, Nootropics, Menopause And F1 - Peter Attia

[DeStrider]

It seems my statin intolerance was worse than I expected. Even 5 mg of Atorvastatin daily caused muscle spasms in my calves and weakness in my thigh muscles. I have switched to 5 mg of Atorvastatin Mon-Wed-Fri. This is much better, and the spasms are gone along with most of the weakness. I guess only time will tell whether this schedule causes problems.

My LDL and ApoB without the statin is 68.
My LDL and ApoB with a daily 5 mg statin is 48.

So, maybe I can hit 55-60 with this new dosing regime? Thoughts?

[RapMet]

@DeStrider

My LDL and ApoB without the statin is 68.
My LDL and ApoB with a daily 5 mg statin is 48.

Never measured ApoB. Does it always equal LDL?

[DeStrider]

My LDL and ApoB are the same at these low levels. When my LDL was higher (120) my ApoB was a bit lower (108).

[mccoy]

@RapMet

Never measured ApoB. Does it always equal LDL?

NO, there is a thread about it (let’s see if I can find it), it hoovers usually in the range of LDL plus or minus 10 mg/dL, but there is no general rule.
Anyway, non-HDL is seemingly the best proxy for ApoB

[adssx]

And if you don’t have access to apoB you can calculate eLDL-TG by yourself and eLDL-TG is apparently even better than apoB, LDL-C and non-HDL-C:

• Formula in mg/dL: Cardiovascular Health - #1407 by RapAdmin
• Formula in mmol/L: Cardiovascular Health - #1410 by adssx

[AnUser]

@adssx

and eLDL-TG is apparently even better than apoB, LDL-C and non-HDL-C:

I find it unlikely it’s better than apoB because of an association study, also a marker that might be partly elevated by obesity or insulin resistance is of no use to me who don’t have that. There’s confounding.