Bettering Me

Tag: blood pressure

  • “Biological Age” Tests Are Mostly Useless. There Are Three Numbers That Actually Tell You Where You Stand

    Written by

    Unpaid Intern

    –

    Epigenetic clocks and biological age panels are the wellness industry’s latest anxiety product. They cost between $200 and $500, spit out a single number – “your biological age is 38 but your chronological age is 45” – and send you into either celebration or despair. The problem is that these numbers correlate weakly with actual hard outcomes in middle-aged populations, change too slowly to guide interventions, and create a false sense that aging is a single metric that can be addressed with a protocol [1].

    There are three different types of epigenetic clocks, and understanding the differences reveals why they are not ready for individual clinical use. The Horvath clock measures methylation at 353 CpG sites and was designed to predict chronological age, not health. It is remarkably accurate at telling you how old you are – which is information you already had. The PhenoAge clock was trained to predict all-cause mortality and is more clinically relevant, but it incorporates routine clinical biomarkers (albumin, creatinine, glucose, etc.) that are more informative on their own than the methylation component. The DunedinPACE clock measures the pace of aging rather than current biological age and is arguably the most useful of the three, but it still changes over months to years – far too slowly to tell you whether your new exercise protocol or sleep intervention is working.

    The fundamental problem is not the science. The methylation patterns are real and interesting. The problem is clinical utility. By the time an epigenetic clock changes meaningfully, you could have measured the actual outcome directly. You could have tested your VO2 max, drawn your ApoB, calculated your HOMA-IR – and gotten feedback you can act on today.

    There are three numbers that actually tell you where you stand regarding your biological trajectory. They are cheap, actionable, and change within weeks of intervention.

    ApoB – your cardiovascular ceiling. This is the single most predictive blood marker for atherosclerotic disease, which remains the primary cause of death in aging populations. If your ApoB is above 90 mg/dL at age 45, your vascular system is accumulating damage even if your LDL-C looks fine [2]. The intervention response – lifestyle modification, dietary change, and if necessary, pharmacological therapy – can be measured in weeks, not years.

    Fasting insulin – your metabolic trajectory. Above 8-10 µIU/mL with normal glucose means your body is producing excess insulin to maintain glucose homeostasis. This is the earliest measurable sign of metabolic aging. It precedes glucose dysregulation by 5-10 years in most people. And it responds to intervention – two resistance sessions per week and a 12-hour overnight fast can reduce fasting insulin by 20-30% in 8-12 weeks.

    VO2 max – your functional ceiling. This is the single best predictor of all-cause mortality in middle-aged and older adults, outperforming every blood marker in head-to-head comparisons [3]. It measures your aerobic capacity directly – not a proxy, not a correlate, not a methylation pattern that may or may not correlate with an outcome. It tells you where you are relative to age-specific norms and whether your training is producing a measurable effect. VO2 max responds to consistent aerobic training at any age, and the changes can be detected within 4-6 weeks of a structured program.

    These three numbers cost approximately $100 total to measure (ApoB: $30-50, fasting insulin: $20-40, VO2 max estimate via submaximal protocol: $0-50). A single biological age panel costs $200-500. For the price of one epigenetic test, you could run the three anchors, get actionable results, and still have money left over.

    Counterpoint: aren’t epigenetic clocks validated? Yes, for certain specific use cases – predicting mortality in terminally ill populations, identifying accelerated aging in chronic disease cohorts, and studying the effects of interventions at the population level. The DunedinPACE clock, for example, has shown that people with higher pace of aging scores have worse physical function in their 40s and 50s [1]. But the effect sizes at the individual level are small enough that knowing your score does not change your clinical management. You would not treat a person with “biological age 40” differently from one with “biological age 48” – you would still optimize ApoB, fasting insulin, and VO2 max in both. The clock adds information that does not change the decision.

    Every dollar spent on a methylation test would be better spent on a DEXA scan and a maximal aerobic test. The simple numbers work. We just do not like how simple they are. We want a single number that tells us whether we are winning, and the epigenetic clock provides that – which is exactly why it is dangerous. It creates the illusion that aging is a static score rather than a dynamic trajectory.

    Bettering Me recommends knowing these three numbers before spending a cent on any biological age panel. The epigenetic clock tells you how old your DNA looks. ApoB, fasting insulin, and VO2 max tell you how old your body is actually functioning. One is entertainment. The other three are information.

    Disclaimer: This post is for inspiration and education, not medical advice. Everyone’s body is different, so please check with your doctor before changing your diet, exercise, or lifestyle routine. By using these tips, you agree to do so at your own risk.

    References

    [1] Bell CG, et al. "DNA methylation aging clocks: challenges and recommendations." *Genome Biology*. 2019;20(1):249.. DOI: https://doi.org/10.1186/s13059-019-1824-y

    [2] Sniderman AD, et al. "Apolipoprotein B Particles and Cardiovascular Disease: A Narrative Review." *JAMA Cardiology*. 2019;4(12):1287-1295.. DOI: https://doi.org/10.1001/jamacardio.2019.3780

    [3] Myers J, et al. "Exercise capacity and mortality among men referred for exercise testing." *NEJM*. 2002;346(11):793-801.. DOI: https://doi.org/10.1056/NEJMoa011858

  • There Are Only Three Blood Tests That Matter for Prevention. The Other Four Are Noise Until These Are Fixed

    Written by

    Unpaid Intern

    –

    The wellness industry has turned annual blood work into an anxiety generator. Lists of seven, ten, fourteen markers – each with an “optimal” range that shifts every time a supplement company publishes a blog post. The result is a population of people who are worried about their homocysteine while their cardiovascular ceiling is unknown, their metabolic trajectory is unchecked, and their inflammatory baseline is a guess.

    The Three Tests at a Glance

    • ApoB: Counts every atherogenic (plaque-forming) particle in circulation — a more accurate cardiovascular risk signal than standard LDL-C alone.
    • Fasting Insulin: Reveals insulin resistance years before fasting glucose rises, catching metabolic dysfunction at the earliest correctable stage.
    • hs-CRP: Measures chronic low-grade inflammation — the modifiable driver that accelerates atherosclerosis independent of lipid levels.

    The hierarchy of prevention blood work is not flat. It has three anchors, and everything else is a distraction until those three are addressed. These three markers form a tripod – each covers a domain no other test covers, and together they answer the three questions that determine whether your prevention strategy is working.

    ApoB is your cardiovascular ceiling. Apolipoprotein B counts every atherogenic particle in circulation – LDL, VLDL, IDL, and Lp(a) – because each of these particles carries exactly one ApoB molecule [1]. LDL-C, the standard metric, estimates the mass of cholesterol inside LDL particles. It does not count the particles themselves. The particles cause plaque, not the cholesterol inside them. ApoB tells you how many plaque-forming particles are circulating, regardless of how much cholesterol they happen to be carrying.

    This distinction matters because two people can have identical LDL-C while one has twice as many atherogenic particles. The person with many small dense LDL particles may have “normal” LDL-C (say, 110 mg/dL) but high ApoB (above 100 mg/dL), and their risk is higher than the person with the same LDL-C but low ApoB [2]. This discordance – the gap between what LDL-C says and what ApoB says – occurs in approximately 15-20% of the population. Those people are being misclassified by the standard panel.

    Fasting insulin is your metabolic trajectory. Fasting glucose is a late-stage indicator – by the time it rises above 100 mg/dL, your pancreatic beta cells have been compensating for years, secreting excess insulin to overcome reduced sensitivity [3]. A fasting glucose of 92 with a fasting insulin of 14 µIU/mL is not “normal.” It is a pancreas working triple shifts to keep the number flat. The threshold worth watching is insulin above 8-10 µIU/mL in the context of normal glucose. The simplest quantification is HOMA-IR: (fasting glucose × fasting insulin) ÷ 405. A value above 2.0 indicates insulin resistance. Above 2.5 signals significant metabolic dysfunction, even with pristine fasting glucose.

    hs-CRP is your inflammatory baseline. High-sensitivity C-reactive protein above 1 mg/L (and especially above 2 mg/L) signals a chronic low-grade inflammatory state that accelerates atherosclerosis independent of lipid levels [4]. The most common cause of elevated hs-CRP is visceral adiposity – fat tissue secretes IL-6, which stimulates hepatic CRP production. But it can also be driven by chronic infection (periodontal disease is a common hidden culprit), autoimmune conditions, or simply an inflammatory diet pattern. hs-CRP is modifiable: weight loss of 5-10% reliably drops it, as does consistent aerobic exercise, omega-3 intake, and eliminating ultra-processed foods. It is the cheapest, most telling measure of whether your lifestyle is producing a net anti-inflammatory effect.

    Homocysteine, vitamin D, thyroid panels, lipoprotein(a) – these matter, but they matter after the three anchors are known. A person with ApoB of 90 mg/dL, fasting insulin of 6 µIU/mL, and hs-CRP of 0.6 mg/L has more prevention information than someone who has all fourteen markers checked but none of these three. The “deep cuts” are for fine-tuning after the structural questions are answered.

    The exception is Lp(a) – lipoprotein(a) – which should be checked once in a lifetime because it is 80-90% genetically determined and does not respond to lifestyle [5]. But Lp(a) is not a substitute for ApoB. It is an additional risk modifier. Check Lp(a) once. If it is high, adjust your ApoB target downward (below 70 mg/dL instead of below 100). If it is low, never think about it again.

    The Bettering Me approach: fix the anchors first. Chase the edges only when the anchors are known and stable.

    The practical protocol for getting these tests. Most standard lab panels do not include ApoB or fasting insulin by default. You need to request them specifically. For ApoB: order “apolipoprotein B” (CPT 82172). For fasting insulin: order “insulin, fasting” (CPT 83525). For hs-CRP: order “C-reactive protein, high sensitivity” (CPT 86141). These three tests add approximately $60-90 to a standard blood draw if your insurance does not cover them. Direct-to-consumer labs like Quest and LabCorp offer them as individual add-ons. Life Extension, Marek Health, and several other direct-access providers offer prevention-focused panels that include all three.

    The retesting cadence. ApoB changes slowly – retest every 6-12 months unless you are on pharmacological therapy, in which case retest at 12 weeks post-initiation. Fasting insulin can change within 8-12 weeks of lifestyle intervention – retest at 12 weeks if you are making significant changes. hs-CRP is the most dynamic – it can shift within 4-6 weeks of weight loss, exercise adoption, or dietary change. A baseline measurement followed by a 12-week follow-up after intervention gives you a clear picture of whether your protocol is working.

    Your homocysteine is not going to kill you. Your ApoB, fasting insulin, and hs-CRP might – or might save you, depending on what you do with the information. Fix the anchors first. Then chase the edges.

    Disclaimer: This post is for inspiration and education, not medical advice. Everyone’s body is different, so please check with your doctor before changing your diet, exercise, or lifestyle routine. By using these tips, you agree to do so at your own risk.

    References

    [1] Sniderman AD, et al. "A meta-analysis of LDL-C, non-HDL-C, and ApoB as markers of cardiovascular risk." *Circ Cardiovasc Qual Outcomes*. 2011;4(3):337-345.. DOI: https://doi.org/10.1161/CIRCOUTCOMES.110.959247

    [2] Otvos JD, et al. "Clinical implications of discordance between LDL-C and particle number." *J Clin Lipidol*. 2011;5(2):105-113.. DOI: https://doi.org/10.1016/j.jacl.2011.02.001

    [3] Kahn SE, Hull RL, Utzschneider KM. "Mechanisms linking obesity to insulin resistance and type 2 diabetes." *Nature*. 2006;444(7121):840-846.. DOI: https://doi.org/10.1038/nature05482

    [4] Ridker PM. "Clinical application of C-reactive protein for cardiovascular disease detection and prevention." *Circulation*. 2003;107(3):363-369.. DOI: https://doi.org/10.1161/01.CIR.0000053730.47739.3C

    [5] Kronenberg F. "Human Genetics and the Causal Role of Lipoprotein(a)." *Cardiovasc Drugs Ther*. 2016;30(1):87-100.. DOI: https://doi.org/10.1007/s10557-016-6648-3

  • The SPRINT MIND Result Is Real – But Your 128 Systolic Is Not the Same as Their 147

    Written by

    Unpaid Intern

    –

    The SPRINT MIND trial produced a genuinely important result: intensive blood pressure control (target below 120 mmHg systolic) reduced the risk of mild cognitive impairment and probable dementia by 19% compared to standard treatment (target below 140 mmHg) [1]. This is one of the few randomized controlled trials showing that a cardiovascular intervention directly reduces dementia risk. It is real, and it should change how clinicians and patients think about the relationship between blood pressure and brain health.

    But the trial’s population matters as much as its result. The average participant in SPRINT MIND was 68 years old with established hypertension – baseline systolic averaging 147 mmHg. Many had existing cardiovascular disease or chronic kidney disease [1]. The trial proved that dropping from 147 to 121 reduces dementia risk in older adults with hypertension. It did not prove that dropping from 125 to 115 does the same thing in a 45-year-old with no cardiovascular history.

    For a 45-year-old walking around with a systolic of 125, the clinical question is not “should I get below 120.” The question is: what is the trajectory?

    A person whose blood pressure has been 118 for a decade and is now trending 125 is not the same patient as someone whose blood pressure has been 145 for a decade and is now trending 125. One is climbing. The other is descending. The same absolute number means a different thing depending on the vector. This distinction is lost in the threshold-based model that guides most clinical decisions – you are either normotensive, prehypertensive, or hypertensive, and the treatment decision fires only when you cross the line.

    The longitudinal data from the Atherosclerosis Risk in Communities (ARIC) study shows that midlife blood pressure trajectories – not single readings – predict cognitive decline decades later [2]. Participants whose systolic rose from 110 to 130 between ages 45 and 55 had higher dementia risk than those whose systolic held steady at 120 across the same window, even though both groups had identical readings at age 55. The trajectory was the signal, not the absolute value.

    This matters because the J-curve hypothesis – the idea that lowering blood pressure too aggressively in certain populations may increase cardiovascular risk – has not been resolved for primary prevention in middle-aged adults [3]. SPRINT MIND’s intensive arm used a multi-drug protocol to achieve its 121 mmHg average. The same pharmacological approach applied to someone whose systolic is 125 and climbing might produce benefit, but the trial did not test that.

    There is also the question of mechanism. Blood pressure damages cerebral small vessels over years, not weeks. The cognitive decline that SPRINT MIND prevented was the result of cumulative microvascular damage in participants who had been hypertensive for decades. A 45-year-old whose pressure is 125 and steady has accumulated far less vascular damage than a 68-year-old whose pressure was 140+ for twenty years. The intervention window is wider. The urgency is lower. But the opportunity for primary prevention is real.

    The framework Bettering Me recommends is trajectory-based, not threshold-based. If your systolic has been within a 5-point band for five years, the intervention is behavioral maintenance: sleep consistency (blood pressure drops 10-20% during deep sleep – the nocturnal dip), sodium sensitivity awareness (test this by tracking pressure for two weeks on high vs low sodium), and aerobic volume above 150 minutes per week (each 1 MET increase in fitness is associated with approximately 5 mmHg lower systolic pressure) [4].

    If your systolic has risen more than 8 points in three years, the intervention is structural – even if you haven’t crossed a “hypertensive” threshold. That means a formal assessment: 24-hour ambulatory monitoring (office readings miss nocturnal hypertension, which is independently predictive of cardiovascular events), dietary sodium assessment, sleep apnea screening (OSA is a common secondary cause of rising pressure trajectories in midlife), and a discussion about pharmacological options if lifestyle alone is insufficient [5].

    The trajectory tells you whether you are approaching a ceiling or retreating from one. SPRINT MIND proved the ceiling matters for dementia. But for most people in their 40s, it is the slope – not the ceiling – that will decide whether they ever reach it.

    A practical note on nocturnal dipping. Blood pressure normally drops 10-20% during deep sleep – the “nocturnal dip.” People whose pressure does not dip (non-dippers) have higher cardiovascular and cognitive risk, independent of daytime readings [4]. The only way to know if you are a dipper is 24-hour ambulatory monitoring. If your office BP is 125/80 but your nocturnal average is 118/75, you are fine. If it is 125/80 and your nocturnal average is 120/78, you are a non-dipper, and your trajectory-based risk is higher than the office reading suggests. This is another reason the standard threshold-based approach misses the signal.

    The sodium sensitivity variable. Approximately 50% of people with normal blood pressure are sodium sensitive – their pressure rises measurably in response to high sodium intake. The others are sodium resistant. The only way to know which you are is to test it: 7-10 days of high sodium (add salt at every meal) vs 7-10 days of low sodium (eliminate added salt, avoid processed foods), measuring BP daily at the same time. If your systolic moves more than 5 mmHg between conditions, you are sodium sensitive, and sodium management is a structural intervention for you, not a marginal one.

    The threshold is a legal category. The trajectory is a clinical signal. Know which one you are looking at.

    Disclaimer: This post is for inspiration and education, not medical advice. Everyone’s body is different, so please check with your doctor before changing your diet, exercise, or lifestyle routine. By using these tips, you agree to do so at your own risk.

    References

    [1] Williamson JD, Pajewski NM, Auchus AP, et al. "Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial." *JAMA*. 2019;321(6):553-561.. DOI: https://doi.org/10.1001/jama.2018.21442

    [2] Gottesman RF, et al. "Midlife Hypertension and 20-Year Cognitive Change: The Atherosclerosis Risk in Communities Neurocognitive Study." *JAMA Neurology*. 2014;71(10):1218-1227.. DOI: https://doi.org/10.1001/jamaneurol.2014.1646

    [3] Bohm M, et al. "J-curve relation between achieved blood pressure and cardiovascular outcomes." *European Heart Journal*. 2010;31(16):1985-1992.. DOI: https://doi.org/10.1093/eurheartj/ehq156

    [4] Cornelissen VA, Smart NA. "Exercise training for blood pressure: a systematic review and meta-analysis." *J Am Heart Assoc*. 2013;2(1):e004473.. DOI: https://doi.org/10.1161/JAHA.112.004473

    [5] Sleep Apnea and BP Trajectory