Cardiovascular Health 2026

#396

I don’t fully agree with this. Yes, inflammation is a driver - but the lipoproteins are still necessary parts.

These companies want to sell these expensive new IL-6 , NLRP3 inhibitors etc. But the fact is, if you can lower atherogenic particles (Lp(a) and Apo-B mostly), you’re most of the way there.

I think the new position paper here sums it up nicely: https://www.jacc.org/doi/epdf/10.1016/j.jacc.2025.08.047

Basically, you want lipoproteins and inflammation to be low. If you can’t get the lipoproteins down, you need to be aggressive in lowering the inflammation, and vice-versa.

If it works, I am curious what makes you want to change? I take the exact same Rosu + Ezetimibe 10mg each (the same combo Donald Trump takes too, apparently). Never had any noticeable side effect, no change in HBA1C, or anything else. So it’s hard to find a justification to change anything IMO.

This is a great paper IMO. The “predisease” simply means a person is on the path to the full disease. It’s not like your BMI is 29 and you’re ok, but once it hits 30, you’re not, or HBA1C of 5.8 vs 6.0%.

I would assume that all of us on this forum would agree about primordial prevention. A hell of a lot easier to keep that glucose down rather than deal with complications of diabetes.

IMO, the single largest (drug-free) lever that many people have for this is resistance training. You can control many things with drugs, but hitting a full body lifting program 2x per week is going to have a huge benefit across pretty much everything they mention - the blood pressure, visceral fat, waist circumference, cardiovascular fitness, glucose disposal etc etc. For the skinny-fat, BMI 23 person with emerging CVD, they don’t need a GLP1RA - they probably just need squats, deadlifts etc.

I asked Claude to pull together studies about weight training interventions on this health markers. Here’s a short selection of highlights, written out by me:

  • A 10% increase in skeletal muscle mass correlates to 12% reduction in pre-diabetes

Various published weight training interventions of 12-24 weeks have shown:

  • HBA1C% reduction of -0.3 to 0.6% (i.e. similar efficacy to metformin)

  • Fasting glucose reduction of 9-15mg/dl

  • Visceral adipose tissue reduction of -0.3 to -0.5%

  • hsCRP reduction of 20-35% in chronic inflammation

  • Blood pressure reduction of -5 mmHg

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#397

What is the “this”?

#398

I have always had mild muscle aches. don’t know if it’s from the statins I have taken and am taking. maybe they will stop if i try pitavastatin

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#399

Ah, sorry my quoting got messed up. It was about the discussion on IL6 testing, and the fancy graphic RapAdmin posted.

#400

My muscle aches stopped with pitavastatin. I had muscle aches even with Atorvastatin 5 mg EOD.

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#401

No worries. For others who might wonder, it’s that one, I guess: Cardiovascular Health 2026 - #320 by RapAdmin

#402

no problem. but my aches started many decades ago when I started on statins. it was 1990. I remember because i was sent to Korea on orders that yr and started them there. a little purple colored one was the first statin of many to follow.

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#403

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https://x.com/changmyung1981/status/2051518874026475658?s=20

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#404

Its an interesting chart. One of my labs gives ApoA-I and I had not looked at it before. I have just looked at it and it varies quite a bit. I think I will try to find how how it varies (in the sense of what exogenous substance causes it to vary). That will have to wait as a project.

I managed to get an LLM to convert my lab tracker to a spreadsheet. I am not sure it worked that well, but this the variation: mg/dL

202.60 167.60 187.30 174.60 178.00 194.50 204.40 201.50 174.00 202.90 164.40 185.70 187.30 190.10 226.40 185.50 198.30 187.30 181.80 200.10 216.30 200.90 190.60 205.20 159.80 177.20 176.40 202.40 172.90 183.10 189.70 168.30 167.80 172.10 165.70 161.60 179.50 200.70 185.60 168.40 173.20 184.10 194.50 176.70 166.20 161.70 169.30 163.60 176.20 176.70 169.20 171.50 171.40 172.50 159.40 150.40 153.30 168.00 158.40 173.90 162.10 166.20 161.20 188.20 190.60

#405

Every statin ranked by efficacy:

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#406

Very interesting. Here is the deep dive on the less known apolipoproteins

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#407

The Genetic Art of Avoidance: Why Your Heart is the Secret to Living Past 100

For decades, the search for “longevity genes” has often felt like hunting for a needle in a haystack. However, new research from the Leiden Longevity Study suggests we may have been looking at the problem backward. Instead of possessing rare “super-genes,” the secret to reaching exceptional ages may lie in the simple absence of genetic “bad luck”—specifically regarding heart health.

By analyzing over 420 long-lived families across three generations, researchers found that the more long-lived ancestors an individual has, the lower their polygenic score (PGS) for coronary artery disease (CAD). This isn’t just a correlation; the study utilized accelerated failure time modeling to demonstrate that a low genetic risk for CAD explains between 14% and 20% of the delay in cardiovascular disease onset seen in these families. Essentially, longevity is fueled by an inherited “shield” against the world’s leading cause of death.

Perhaps most striking was the discovery of a specific cholesterol-metabolism-PGS. While the APOE gene is often cited as the primary driver of cardiovascular longevity, this study identified a separate cluster of 49 to 52 SNPs related to lipid handling that predicted survival even after APOE was removed from the equation. This suggests that the way our bodies manage lipoproteins—beyond just the famous “longevity alleles”—is a fundamental pillar of human lifespan.

For those aiming for the “nonagenarian” finish line, the message is clear: your family’s history of heart health is a quantitative predictor of your own aging trajectory. While we cannot yet edit our polygenic scores, this data reinforces that cardiovascular maintenance is the primary mechanical hurdle between a standard lifespan and a century of health.

Actionable Insights

  • Prioritize Advanced Lipid Profiling: Since cholesterol metabolism pathways were found to be central to 90+ survival independent of APOE , biohackers should move beyond standard LDL-C tests. Focus on ApoB , LDL particle number , and triglyceride levels , as these reflect the underlying lipoprotein signature associated with familial longevity.

  • Quantify Familial Risk: Use the Longevity Relatives Count (LRC) score logic. If more than 30% of your ancestors reached the top 10% of their birth cohort’s survival, you likely carry a lower “genetic burden” for CAD.

  • Targeted Cardiovascular Intervention: Because CAD risk alleles explain 20% of the delay in disease onset, aggressive management of cardiovascular “soft” markers (blood pressure, arterial stiffness) is the most evidence-based path to mimic the “protected” phenotype of long-lived families.

  • Contextualize Genetics with Environment: A PGS is a prediction, not a decree. The 80% of cardiovascular disease onset left unexplained by this study is likely driven by gene-environment interactions —meaning lifestyle choices can still override high-risk genetic scores.

Source:

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Full stack optimization based on the findings from the genetic deep dive reports
#408

The Social Scaffolding of Longevity: Why Your Mindset and Education Dictate Your Cardiovascular Age

While chronological age is a fixed count of years, biological age is a variable rate of decay. New research from the Inlife-Aging Project suggests that for middle-aged and older adults, the speed of this decay is significantly influenced by psychosocial architecture. By utilizing the American Heart Association’s “Life’s Essential 8” (LE8) framework—a metric covering diet, activity, sleep, nicotine exposure, BMI, lipids, glucose, and blood pressure—researchers identified that most individuals reside in a “moderate” cardiovascular health (CVH) purgatory.

The “Big Idea” here is the “weathering” hypothesis: chronic psychosocial stressors, such as financial hardship or low educational attainment, act as biological accelerators. These stressors do not just make life difficult; they physically degrade the body’s physiological maintenance capacity through “inflammaging” and the accumulation of senescent cells.

The study found a stark demographic divide. Middle-aged women emerged as the “longevity elite,” exhibiting the most favorable CVH profiles, likely due to higher engagement in protective health behaviors. Conversely, older men scored the lowest, particularly in health factors like blood pressure and glucose regulation. Interestingly, while participants excelled at maintaining physical activity and sleep, their diet quality was a statistical disaster, scoring the lowest among all metrics.

Ultimately, the strongest predictors of a resilient heart were not just physical metrics, but educational attainment and “self-rated health”—how a person perceives their own vitality. This suggests that your internal narrative and your access to health literacy are as much a part of your cardiovascular system as your arteries.

Actionable Insights

  • Prioritize Diet Quality: Diet was the lowest-scoring component (40.8 ± 31.7). For longevity seekers, this is the highest-leverage area for improvement. Focus on high-quality, nutrient-dense intake to move from “moderate” to “high” CVH.

  • Leverage Educational Literacy: Educational attainment (≥ 12 years) strongly correlated with better BMI, glucose, and blood pressure. Actively seeking health education and literacy can act as a buffer against environmental stressors.

  • Monitor Subjective Vitality: Your “self-rated health” is a potent indicator of physiological reserve. If you perceive your health as “Poor-Fair,” it correlates with lower physical activity and worse clinical markers. Addressing the psychological perception of health is as vital as the physical reality.

  • Mitigate Depressive Symptoms: Clinical depressive symptoms were negatively associated with physical activity, nicotine exposure, and sleep health. For those in the 50–79 age bracket, mental health maintenance is a direct cardiovascular intervention.

Context

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#411

How Cardiovascular Health Calibrates the GrimAge Clock

Chronological age is a fixed variable, but biological age is proving to be a highly plastic metric. Research from the INSPIRE-T cohort in France reveals a critical, bidirectional relationship: your cardiovascular health (CVH) doesn’t just prevent heart attacks; it actively slows the molecular ticking of your epigenetic clock. Conversely, an accelerated “GrimAge” clock is now identified as a potent risk factor for future cardiovascular events, independent of how many birthdays you have celebrated.

The study analyzed nearly 1,000 individuals aged 20 to 100, measuring their adherence to the American Heart Association’s “Life’s Essential 8” (LE8)—a score covering diet, activity, sleep, nicotine, BMI, lipids, glucose, and blood pressure. The results were stark: those with optimal cardiovascular health showed significantly younger biological ages. Interestingly, this protective effect was most pronounced in men and younger individuals, suggesting that the “longevity dividends” of a healthy lifestyle are greatest when established early in life.

While five different epigenetic clocks and one inflammatory clock (iAge) were tested, GrimAge emerged as the superior predictor. This clock is unique because it incorporates “surrogate” markers of plasma proteins and smoking history that are directly linked to morbidity and mortality. The data suggests that by optimizing behavioral factors—specifically smoking cessation and BMI—you can effectively “re-program” your epigenetic profile to reflect a younger, more resilient phenotype.

Actionable Insights

To maximize longevity and slow epigenetic aging, the data suggests four primary levers:

  • Aggressive Smoking Cessation: Nicotine exposure was the strongest behavioral driver of accelerated epigenetic aging across both sexes. Moving toward a “non-smoking ideal” provides the most significant reduction in GrimAge.

  • Early-Life Intervention: The association between cardiovascular health and slower aging is significantly stronger in individuals under 40. Prevention must start decades before clinical symptoms appear. [Confidence: High]

  • Sex-Specific Optimization: Men appear to derive a greater “epigenetic discount” from physical activity, optimal sleep, and blood pressure control than women. For women, BMI and smoking were more dominant predictors.

  • Targeted Biomarker Monitoring: Use the GrimAge clock for biological age testing. Other clocks like Hannum or Horvath may not capture the specific cardiovascular burden reflected in your epigenetic signature. [Confidence: High]

Source:

Related Reading:

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#412

@CronosTempi Is there any reason why we can’t take 6 mg of Pitavastatin?

#413

Max dose is 4mg. They don’t make 6mg pills.

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#414

The highest dose pitavastatin that is marketed is 4mg. When they developed this statin, they decided to position it as a medium intensity statin in the market. There were trials of 8mg doses with apparently good results, but because the MOA was somewhat novel, they decided to go with 4mg as max, out of an abundance of caution. As a result, ever since, all the clinical data from the patients out there have been from 1/2/4 mg doses. Therefore other than the studies with 8mg there simply are no large scale longitudinal data sets for higher doses. So if taking higher doses 6, 8mg you can’t point to long term outcomes. It’s an unknown. Probably it’s fine, and there certainly are people (including on this site) who take 6mg or higher, but nobody can say “here are the outcomes for 6/8mg”. And most physicians will not prescribe doses without data and not marketed by the pharma company. Bottom line, it represents a gamble. Most people are not going to gamble.

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#415

If you try this higher dose level, please post pre and post LDL-C numbers so we can identify the benefit (or lack thereof).

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#416

What I found interesting was the fact that doubling the dose from 1mg to 2mg it barely moved the needle, only about 10% lower. I might stick with 1mg (cheaper and hopefully less sides) as I happen to be in the camp that believes in a level of 60-70 as being optimal (of course assuming other markers LP-a and APO-B etc. remain low also). if for nothing else other than for the fact that time and again we see old/centenarian people with higher-than-normal LDL-c yet they chug along just fine. I still can’t fully wrap my head around the idea that we should shoot for LDL-c of zero (or very low 20-40) LOL unless there was a mistake in the way we evolved. Just MO.

#417

20% of people seem naturally protected from high LDL-C for various reasons. 80% of people are not.

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