Cardiovascular Health

World_Traveler · May 2, 2025, 6:44am

The decision to discontinue the Repatha® Pushtronex® system was made to uphold the high standards Amgen holds for patient experience , focusing on delivering optimal care for patients with cardiovascular disease and hyperlipidemia (high bad cholesterol).

Dr Attia takes PCSK9 Inhibitors:, are probably needed to get lower. Very expensive 43 is excellent. Crestor 5 mg gives you appx. 85% of benefit. 10 mg 100% You can buy a combo pill of Crestor/Ezetimibe 10/10 for 1/2 cost. Good Luck on Lp(a) EZ is good, but BA?

CronosTempi · May 2, 2025, 7:00am

Endothelial cell-related genetic variants identify LDL cholesterol-sensitive individuals who derive greater benefit from aggressive lipid lowering

https://www.nature.com/articles/s41591-025-03533-w

CronosTempi · May 2, 2025, 8:38am

Pharmacodynamic effect of bempedoic acid and statin combinations: predictions from a dose–response model

"Dose–response models predicted that combining bempedoic acid with the lowest statin dose of commonly used statins would achieve a similar degree of LDL-C lowering as quadrupling that statin dose; for example, the predicted LDL-C lowering was 54% with atorvastatin 80 mg compared with 54% with atorvastatin 20 mg + bempedoic acid 180 mg, and 42% with simvastatin 40 mg compared with 46% with simvastatin 10 mg + bempedoic acid 180 mg.

Conclusion

These findings suggest bempedoic acid combined with lower statin doses offers similar LDL-C lowering compared with statin monotherapy at higher doses, potentially sparing patients requiring additional lipid-lowering therapies from the adverse events associated with higher statin doses."

Bicep · May 2, 2025, 1:05pm

My wife said the same thing. Duh. But Lustgarten in his book pretty much takes it as a result of the vitamin k1. He goes on and on about it. Hard to prove it without testing with the vitamin instead of the vegetables. I agree this study is not proof.

John_Hemming · May 2, 2025, 1:22pm

They say they have adjusted for confounders, but we would need to see the detailed calculations to assess as to whether the adjustment is reasonable.

what effects on mortality of human beings does vitamin K1 have

ChatGPT said:

Vitamin K1 (phylloquinone), primarily known for its role in blood clotting, has also been studied for potential effects on mortality, especially cardiovascular-related. Here’s what is known based on current research:

1. Cardiovascular Mortality

Some studies suggest that higher dietary intake of vitamin K1 may be associated with a reduced risk of cardiovascular disease (CVD) and mortality. This is likely due to its role in activating matrix Gla-protein (MGP), which helps prevent vascular calcification.
However, evidence is mixed, and the associations are generally stronger for vitamin K2 (menaquinones), which has a more direct effect on vascular health.

2. All-Cause Mortality

Observational studies (like the EPIC and Rotterdam studies) have shown a possible inverse association between vitamin K1 intake and all-cause mortality, but the data is not consistent or conclusive.
Most of these findings are associative, not causal, and may reflect generally healthier diets rather than a specific effect of vitamin K1.

3. Cancer-Related Mortality

Some preliminary research has looked at vitamin K1’s role in reducing cancer progression, but evidence is weak and limited compared to vitamin K2.

Summary:

Vitamin K1 may have modest beneficial effects on mortality, particularly cardiovascular mortality, but the evidence is not strong or definitive.
The more pronounced effects on health and mortality have been observed with vitamin K2, not K1.
More randomized controlled trials (RCTs) are needed to establish any direct impact.

Beth · May 2, 2025, 2:01pm

Thank you for the clip! (I have to learn how to do that!)

I’m pro statin, but I don’t feel well on them. Him sharing that you get 85% of the benefit from low dose statins is incredibly helpful and I’ve shared that with my family whose docs just keep raising it without suggesting EZ etc.

I was on repatha when it first came out a few years ago, and then I went on EZ last summer, and then started BA over the winter in an effort try to get my apob even lower.

Many years ago, I was told that I shouldn’t bother with EZ because, due to my diet, I’m not really consuming anything for it to work on…. IDIOTS

My apob 30 goal was advice from Attia (I messaged him and he kindly responded)

Davin8r · May 4, 2025, 12:51pm

It’s looking more and more like anyone with CVD or at high risk for it, should be on an SGLT2i:

RapAdmin · May 5, 2025, 3:27pm

SGLT2 inhibitors dropped my Uric Acid levels through the floor…

New open access paper:

Long-term cardiovascular risk and mortality associated with uric acid to HDL-C ratio: a 20-year cohort study in adults over 40

Cardiovascular diseases (CVD) and mortality remain significant public health challenges, especially among middle-aged and older adults. However, their relationship with Uric Acid to High-Density Lipoprotein Cholesterol Ratio (UHR) has not been extensively studied in the US population. This study aimed to examine these associations in adults aged ≥ 40 based on the National Health and Nutrition Examination Survey (NHANES) 1999–2018. 29,742 participants’ data in NHANES between 1999 and 2018 were retrospectively analyzed. Multivariable logistic regression, Cox proportional hazards models, restricted cubic spline (RCS) analyses, and subgroup analyses were used to assess the associations between UHR and various CVD outcomes. Among the participants, 4,505 (15.15%) reported a history of CVD. A positive association was observed between UHR and the risk of total CVD, including coronary heart disease, heart attack, heart failure, angina pectoris, and stroke (P all < 0.05). UHR was associated with increased risks of all-cause mortality (HR = 1.02, 95% CI: 1.02–1.03) and CVD-specific mortality (HR = 1.03, 95% CI: 1.02–1.05). UHR had a linear dose-response relationship with CVD and a nonlinear relationship with all-cause mortality by RCS analyses. Subgroup analyses confirmed that these associations remained stable across different groups. The findings highlight UHR as a significant predictor of CVD risk and mortality in middle- and older-age adults. Given its strong association with adverse health outcomes, UHR can be a valuable indicator in facilitating the early identification of individuals at elevated cardiovascular risk.

https://www.nature.com/articles/s41598-025-99205-3

Independent and joint associations of sedentary behaviour and physical activity with risk of recurrent cardiovascular events in 40,156 Australian adults with coronary heart disease

https://www.sciencedirect.com/science/article/pii/S266666772500073X?via%3Dihub

CronosTempi · May 9, 2025, 4:15pm

As always with such associations, reverse causality is a consideration. Perhaps those who had fatal or MACE outcomes were just sicker and less capable of physical activity.

I say this as I just skipped a heavy exercise session, because my knee was bothering me, and I didn’t want to risk an injury. I’m off rapa for another couple of weeks. As soon as I feel better, I will resume my exercise program. Meanwhile an observer could say, “gee, he’s exercising less intensively, and we see that his knee is bothering him, he should’ve been exercising intensively”.

All of this on a much bigger scale, of course. The runner who developed terminally bad knees, quits running, while the one who because of lucky genetics has good knees, continues running.

Now, if you get intervention studies, we can try to chicken and egg this association.

CronosTempi · May 9, 2025, 5:06pm

This is a great 5 minute presentation on hsCRP and CVD, and why it’s important to tackle this issue.

Universal Screening for hsCRP commentary by Dr. Paul Ridker, MD, MPH

amuser · May 9, 2025, 5:46pm

Counterpoint: Universal screening for IL6?

CronosTempi · May 9, 2025, 7:45pm

This dovetails very nicely with the studies showing Lp(a) as a risk factor in the context of hsCRP and IL-6. There were a number of studies showing that elevated Lp(a) was highly MACE causative when hsCRP is elevated (above 2mg/L) - an example is a paper @BarryAllen posted in the thread “CVD and high Lp(a) levels”:

High-sensitivity C-Reactive Protein Modifies the Cardiovascular Risk of Lipoprotein (a): Multi-Ethnic Study of Atherosclerosis

“Lp(a)-associated ASCVD risk is observed only with concomitant elevation of hsCRP. Individuals with concomitant presence of elevated Lp(a) and systemic inflammation have greater ASCVD risk and all-cause mortality, thus may merit closer surveillance and more aggressive ASCVD risk management.”

However, things are not so simple as I noted in that thread. First, I cited a paper that found that:

“In both primary and secondary prevention populations, higher Lp(a) was associated with increased cardiovascular risk independent and regardless of hs-CRP”
https://jamanetwork.com/journals/jamacardiology/fullarticle/2814836

But also, and this is where IL-6 is tied in:

Inflammation, Lp(a) and cardiovascular mortality: results from the LURIC study

“Participants were predominantly male, with a mean age of 62.6 years. Extremely high Lp(a) (> 100 mg/dL) was associated with increased cardiovascular mortality (HR 1.5, 95% CI 1.06-2.12) compared to Lp(a) < 50 mg/dl. Both hsCRP (> 2 mg/L, HR 1.39, 95% CI 1.08-1.79 third vs. first interval) and more so IL-6 (HR 1.92, 95% CI 1.64-2.23, upper vs. lower half), were independently associated with higher CVD mortality. While hsCRP did not increase the Lp(a)-CVD mortality in stratified analysis, high IL-6 conferred an increased risk at Lp(a) levels > 100 mg/dL (HR 1.25, 95% CI 1.09-1.44).”

Bottom line, IL-6 is certainly a key inflammatory marker which appears causative in CVD. The poster @BarryAllen also provided a link on how to control IL-6 in that thread.

RapAdmin · May 9, 2025, 7:59pm

More good news on the Shingles vaccine:

adssx · May 10, 2025, 7:27am

Discussed here: Shingles: Live Zoster vaccination = 23% risk reduction in MACE

Get the shingles vax! (even if you’re young)

relaxedmeatball · May 10, 2025, 10:08am

IMO, I don’t think hsCRP and IL-6 is a something where you need to choose or decide which is better. It’s likely that they both move in the same direction a lot of the time, but one might be a more useful biomarker for acute or chronic conditions. Obviously CRP is a bit more “standard” to measure on most blood test menus, but IL-6 isn’t particularly difficult either. The issue IMO is that both are incredibly non-specific; they’ll raise after a vigorous workout session, or if you catch a respiratory infection, or if you have auto-immune issues, etc etc. They’re also not specifically bad or harmful. Both of them are biologically important; CRP itself is part of the immune response, and IL-6 also plays a lot of roles in responses to injury and infection. So seeing a rise in IL-6 could be a perfectly normal thing because you’re effectively dealing with some infection or other.

Beth · May 10, 2025, 1:15pm

For whatever reason, I got the old-timey shingles vax aprox 15 years ago (before I was 50, and I just walked into the drugstore with no rx).

Last year I also got Shingrix because I learned the old timey one was not nearly as effective. I was previously thinking, darn, I got a vax that wasn’t that helpful, and too bad I didn’t wait for the invention of Shingrix… And now I feel extra lucky I got two kinds and maybe this has slightly decreased my chance of an MI.

For those having trouble getting the vax if you are under 50, do you really need an rx if you are in the US, and you can’t simply walk into the drugstore and say I’m immunocompromised? I didn’t’ t have an rx for Shingrix, but I was over 50 for that one.

Paul · May 10, 2025, 3:14pm

interesting, mine are also quite low since starting jardiance

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