Did we/study establish what an optimal NHHR is? and it is obvious that cohorts in highest quarter percentile would be at VERY high risk since to have a NHHR above 4.5 it would mean their LDL-C is well over 150, since HDL is for most people in the range of 40-60. In other words, I think this study is just proving the obvious.
As an example, at my worst reading I had what I considered poor numbers total 175, LDL-c 124 and HDL-C 39 and even with these numbers my NHHR of 3.5 (last test my NHHR is 1.9) would still be below the mean for the survivors, so this would mean I’m good whereas looking at LDL-C alone tells a different story. So, am I not better off looking at the LDL-C still?
To be fair I’m only going by the summary you posted and did not click on the link for details. .
I wonder if ApoB/HDL-c would be an even better marker for risk ?
When asked, the Medical AI, OpenEvidence.com states: The American College of Cardiology/American Heart Association 2026 Dyslipidemia Guideline recommends apoB alone as the preferred measure of atherogenic lipoprotein burden for ASCVD risk assessment and does not endorse the ApoB/HDL-C ratio as a recommended metric. The guideline emphasizes that apoB directly quantifies the number of atherogenic particles (one molecule per LDL, VLDL, and Lp(a) particle) and predicts ASCVD risk more accurately than LDL-C, particularly in settings of discordance — most commonly in individuals with cardiometabolic disease, diabetes, and/or triglycerides ≥150 mg/dL. In primary prevention, only apoB remained significantly associated with incident MI when assessed together with other atherogenic lipid measures (adjusted HR per 1 SD: 1.27; 95% CI, 1.15–1.40; P 0.001). The guideline recommends integrating apoB into routine risk stratification, supported by large cohort studies and meta-analyses demonstrating its superior predictive value compared with traditional lipid markers. No recommendation is made for lipid ratios incorporating HDL-C as a denominator for apoB-based risk assessment.
I suspect they did not evaluate ApoB/HDL-C for its strength as a risk indicator.
So I went to a cardiologist recommended by my doc. He couldn’t figure out how to get me a CCtA with Cleerly paid by medicare so he sent me to her. She got me a echo and ordered a CCTA, but I asked about Cleerly and she hates the machines. No AI for this one. She practically yelled at me. She said she could read better than the machine and the machine doesn’t care anyway. She offered me Leqvio probably because she correctly guessed I’m a person that might back out of the other kind. Thinks she can get it for free. We’ll see what happens after the CCTA, it’s in a couple weeks.
All I can add is that machines are helping the farmer with things I never thought would work. I’m not worried about being replaced though. It can’t do a round without me. But at the end of the day I’m less tired and get more done.
I really think that she could do more working with the machine. More people could see her and her advice could be better. Machines scan more carefully and don’t make mistakes. I’m sure they need to be checked manually, but it would take less time.
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.
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%
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.
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
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.
Impact Evaluation: The impact score of this journal is 7.5 (2023 JIF), evaluated against a typical high-end range of 0–60+ for top general science, therefore this is a High impact journal within the specific field of Geriatrics and Geroscience.
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.
Institution: MOVE-IT Research Group, Universidad de Cádiz.
Country: Spain.
Journal Name: GeroScience.
Impact Evaluation: The impact score of this journal is 5.6 (2024 CiteScore), evaluated against a typical high-end range of 0–60+ for top general science, therefore this is a High impact journal within the specialized field of geroscience.
