#516

~2-3bpm. Not a lot. Oura reports min overnight as RHR: 53bpm. Whoop reports average overnight: 60bpm. Whoop overall average heart rate is 70bpm (I think this includes exercise). All went up 2-3 beats with the tirzepatide/stimulants, and now back down with ivabradine. No side effects. Tinnitus is better, which I didn’t know beforehand is one potential benefit. I just happened to notice my tinnitus was much better and sometimes totally gone and attribute it to the Ivabradine based on the clinical/anecdotal evidence that it can help with that.

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#517

Playing with a thread summary delivered through an AI created podcast from NotebookLM. Give a listen, very interesting as a way to catch up on a thread.

https://notebooklm.google.com/notebook/3cec1e5b-faaa-4e58-aa41-f13a55ee6056/audio

Seems like the tool sure spends a lot of time on giving warnings etc, seemed to wrap up the conversation 3 times.

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#518

So a pretty small effect of Ivabradine then. Maybe because your RHR wasn’t much higher to begin with.

#519

Holy cow. The audio here is AI generated from this thread? I’m blown away

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#520

That would make sense. I primarily took it to see if it could reduce some of the dysautonomia/POTS symptoms I started experiencing that are likely a result of a minor bout of long covid (exacerbated by stimulants and possibly GLP-1s). It does seem to work well for that.

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#521

Suloxide, a mix of purified glycosaminoglycans?

Sulodexide, traded as Aterina, is a highly purified mixture of glycosaminoglycans composed of heparan sulfate (80%) and dermatan sulfate (20%). - (Sulodexide - Wikipedia)

Meta-analysis on BP lowering:

Considering the effects of glycosaminoglycans on endothelial function and sodium homeostasis, we hypothesized that sulodexide may lower blood pressure (BP). In this meta‐analysis, we therefore investigated the antihypertensive effects of sulodexide treatment.

Methods

We selected randomized controlled trials that investigated sulodexide treatment of at least 4 weeks and measured BP at baseline and after treatment. Two reviewers independently extracted data on study design, risk of bias, population characteristics and outcome measures. In addition, we contacted authors and pharmaceutical companies to provide missing data.

Results

Eight studies, totalling 3019 subjects (mean follow‐up 4.4 months) were included. Mean age was 61 years and mean baseline BP was 135/75 mmHg. Compared with control treatment, sulodexide resulted in a significant systolic (2.2 mmHg [95% CI 0.3, 4.1], P = 0.02) and diastolic BP reduction (1.7 mmHg [95% CI 0.6, 2.9], P = 0.004). Hypertensive patients displayed the largest systolic BP and diastolic BP reductions (10.2/5.4 mmHg, P < 0.001). Higher baseline systolic and diastolic BP were significantly associated with larger systolic (r 2=0.83, P < 0.001) and diastolic BP (r 2=0.41, P = 0.02) reductions after sulodexide treatment. In addition, systolic (r 2=0.41, P = 0.03) and diastolic BP reductions (r 2=0.60, P = 0.005) were significantly associated with albuminuria reduction.

Conclusion

Our data suggest that sulodexide treatment results in a significant BP reduction, especially in hypertensive subjects. This indicates that endothelial glycosaminoglycans might be an independent therapy target in cardiovascular disease. Future studies should further address the BP lowering potential of sulodexide.

Sulodexide is a highly purified mixture of glycosaminoglycans (GAGs) that is currently marketed in a number of countries in Europe, South America and Asia for various cardiovascular conditions. GAGs are large, negatively charged, linear polymers that are present on the surface of all endothelial cells and in the extracellular matrix. Here, GAGs interact with a wide range of processes that are involved in the development of cardiovascular disease, including shear mediated nitric oxide (NO) production and non‐osmotic sodium storage 6. Sulodexide has been shown to improve endothelial function and lipid profiles, exert anti‐inflammatory, anti‐thrombotic and fibrinolytic activity, inhibit leucocyte adhesion and diminish platelet aggregation 7. Because of these vasoprotective effects, sulodexide has been studied in numerous clinical trials. For instance, sulodexide has been shown to decrease claudication symptoms in peripheral artery disease patients and to prevent atherothrombotic events after acute myocardial infarction 8, 9. In addition, a series of small studies demonstrated that sulodexide decreased albuminuria 10. However, two recently performed large randomized controlled trials could not reproduce these findings 11, 12. Noticeably, no clinical trials have thus far investigated the antihypertensive potency of sulodexide.

The BP lowering effects of sulodexide may relate to both increased NO production and non‐osmotic sodium storage

Non‐osmotic sodium storage may also contribute to the antihypertensive potency of sulodexide 6. Sulodexide consists of negatively charged GAGs, which have been shown to be able to bind and osmotically inactivate sodium ions in the skin interstitium 36, 37, 38. In addition, GAGs in the ESL have been shown to be able to bind sodium under flow conditions 39. Considering the large systemic volume of the ESL, non‐osmotic sodium storage in the ESL may have significant implications for BP and extracellular volume regulation 40. Sulodexide may therefore increase the capacity for non‐osmotic sodium storage and prevent sodium from deteriorating endothelial cell function or expanding extracellular volume and causing BP to rise

A cardiovascular outcome trial in 3986 myocardial infarction patients demonstrated that sulodexide was able to reduce mortality and reinfarction rate compared with standard therapy, excluding antiplatelet and anticoagulant therapy

Is it safe, is this a good source?

Toxicity

Sulodexide seems to be well tolerated. Most adverse effects reported are related to the GI system and seem to be transient in nature. Among others adverse reactions are diarrhea, epigastralgia, dyspepsia, heartburn and dizziness. Allergic reactions, such as skin rash, have also been reported but are very rare. (https://go.drugbank.com/drugs/DB06271)

What do people think? Has anyone heard of this before?

BP and Sodium is more complicated (tissue sodium accumulation e.g in skin might play a role).

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Salt / Sodium's role in accelerating aging
#522

Blood pressure and the brain: the conundrum of hypertension and dementia 2025

Many studies have begun to examine the cumulative burden of hypertension in late life through examination of younger to middle-aged adults. In the Coronary Artery Risk Development in Young Adults (CARDIA) study, every 5 mmHg increment in time-weighted average (TWA) of SBP in young adults is associated with approximately 1-year greater brain age. Likewise, participants with TWA BP over the recommended guidelines (SBP <120 mmHg, DBP <80 mmHg) had on average 3-year greater brain age compared to age peers with healthy BP.24 Additionally, individuals with moderate to increasing BP trajectories were more likely to have higher abnormal WM volume and/or lower grey matter CBF.25
In more recent years, the findings from the SPRINT-MIND trial have received considerable attention showing that intensive BP control (<120 mmHg) did not significantly reduce the risk of probable dementia as compared to standard BP control (<140 mmHg) in individuals with hypertension, but did find that intensive BP treatment reduced the risk of mild cognitive impairment (MCI) and the combined rate of MCI or probable dementia.
More comprehensive evidence came from a recent meta-analysis of 14 clinical trials (96 158 participants), including SPRINT-MIND,45 which found that BP lowering with anti-hypertensive medication compared to control was associated with a lower risk of dementia or cognitive impairment, although with a very small absolute risk reduction (0.39%).
Beyond the broad potential effects of anti-hypertensive medications, it is important to further explore whether certain class-specific anti-hypertensive drugs show a more beneficial effect in reducing dementia risk and if different effects of different drugs might explain the inconsistent trial results (SPRINT-MIND, for instance, allowed all anti-hypertensive drugs). […] A recent meta-analysis also concluded that angiotensin II receptor blockers, along with calcium channel blockers, could significantly reduce dementia risk.51 A drug’s ability to cross (vs. not cross) the blood–brain barrier (BBB) is also likely to impact its role in reducing cognitive decline: BBB-penetrant renin–angiotensin drugs appear to reduce cognitive decline in older adults with normal cognition more than do drugs that are not BBB penetrant.
Hypertension makes the BBB leaky
One of the outstanding questions in the field is whether hypertension-induced BBB leakage is involved in the initiation of dementia or is a consequence of the complex neurovascular pathology.150 The answer remains unclear, but many studies have used young hypertensive animals to study this mechanism. Findings have shown a higher BBB leakage in cardiovascular regulatory regions in young hypertensive rats compared to normotensive controls.

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#523

Nebivolol gives me crazy nightmares if i take it after 6:00pm so I’m thinking about taking it in the morning then carvedilol afternoon to see how it works out :thinking:

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#524

Beta blockers can mess up with melatonin and trigger RBD ( https://academic.oup.com/sleep/article/45/Supplement_1/A346/6592654 ). Why are you using a beta blocker? They’re not the first line treatment for blood pressure and they come with many issues (glycemic dysregulation being another one).

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#525

I went to my yearly checkup yesterday and blood pressure was 108/68 !! The nurse checked several times and also several times during my stress test. Afterward the doc wanted to know if I was on something to increase my NO. I said just celery and he shook his head. Also I was still conversational after 15 minutes of BRUCE protocol and my heart rate was 140. It took me till I got home to think what the difference might be. I’m pretty sure it was the chelation, which has been shown to lower blood pressure.

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#526

Are you taking minoxidil? Other medicine?

#527

I’ve never taken anything for BP. All my drugs are for getting rid of glucose. Acarbose rarely with carbs because I rarely have many carbs. Empag just to use them up because this drug wears me out. I’m going back on Dapag as soon as I order again. And Colchicine.

Pioglitazone and Bempedoic acid are both bad for all cause mortality. And Pio does seem to interfere with Rapa in ways I don’t understand. So though I have them I don’t take them for now.

#528

ADHD is a chronic neurodevelopmental disorder that significantly affects life outcomes, and current treatments often have adverse side effects, high abuse potential, and a 25% non-response rate, highlighting the need for new therapeutics. This study investigates amlodipine, an L-type calcium channel blocker, as a potential foundation for developing a novel ADHD treatment by integrating findings from animal models and human genetic data. Amlodipine reduced hyperactivity in SHR rats and decreased both hyperactivity and impulsivity in adgrl3.1−/− zebrafish. It also crosses the blood-brain barrier, reducing telencephalic activation. Crucially, Mendelian Randomization analysis linked ADHD to genetic variations in L-type calcium channel subunits (α1-C; CACNA1C, β1; CACNB1, α2δ3; CACNA2D3) targeted by amlodipine, while polygenic risk score analysis showed symptom mitigation in individuals with high ADHD genetic liability. With its well-tolerated profile and efficacy across species, supported by genetic evidence, amlodipine shows potential to be refined and developed into a novel treatment for ADHD.

Validation of L-type calcium channel blocker amlodipine as a novel ADHD treatment through cross-species analysis, drug-target Mendelian randomization, and clinical evidence from medical records 2025

Is there any other traditional longevity drugs (e.g BP lowering) with effects on e.g cognition for ADHD, depression, or schizophrenia (all are genetically correlated)?

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#529

The devil is in the details when it comes to BA and all cause mortality as well as cardiovascular mortality depending on the group treated. It is better for primary than secondary prevention. Elevated gout and renal problems. Polypharmacy indicated, seems to me.

For pioglitazone, it’s pretty clear that ACM is lower in treated diabetics, but of course off label use (such as folks here might use) is less studied. I certainly wouldn’t take it with rapamycin, but otherwise would consider short term treatment (a few months) for specific goals. And while caution advised while on rapamycin, polypharmacy seems helpful in combination with SGLT2i like empagliflozin. YMMV.

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#530

Statistical illiteracy is also bad for all cause mortality.

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#531

I have a rule that if I laugh at a post I have to like it, no matter why. Laughter increases both healthspan and lifespan, this is important.

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#532

Interesting regarding amlodipine. I’m taking it and didn’t notice any benefits other than BP lowering.

Other interesting ones:

  • Telmisartan
  • Lithium orotate
  • Selegiline
  • SGLT2i
  • Rapa + ketamine

See: 抑郁症和心理健康：你用什么？

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#533

@DrFraser and others - My SBP tends to vacillate between 115 (resting) and 138 (after moderate exercise - like walking quickly (rushing)) while my DBP and heart rates are static at 80-81. Do you think it makes sense to add amlodipine 5 mg to reduce both resting and non-resting SBP?

I just did a test at the doctor’s office where I was rushing to get there and 5 minutes after arriving my SBP was 138. I waited in the office for about 15-30 minutes while resting and my SBP dropped to 115 on a re-test. Do you think the Dr.'s BP machine is defective due to the large variance? Thank you in advance.

This is why that 23 mm HG variance worries me…

Is a Fluctuating Blood Pressure Serious?

Normal variations may differ by person. However, large variations may indicate a health condition. One study looked at patients taking blood pressure medicine. They found variations of more than 14 mm Hg in systolic pressure were associated with a 25% increased risk of heart failure.11

#534

I don’t have a link handy to studies, but here’s an article on orthostatic hypertension. IMO the answer here is more widespread use of 24 hour blood pressure monitors to see trends throughout the day. I’m not aware of any studies that have linked 24 hour blood pressure readings to risk, however.

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#535

There’s a growing body of evidence showing that blood pressure variability (intra day or between days) is as important if not more than BP readings at a certain point in time.

For instance from the 2024 Lancet report on dementia prevention: Dementia Prevention - 2024 report of the Lancet standing Commission - #5 by adssx

These meta-analyses did not cover blood pressure variability, but a cohort study (n=2234; aged ≥65 years) measured blood pressure variability with assessments over 3, 6, 9, and 12 years and reported that each unit increase in systolic variability was associated with increased risk of dementia, with HRs ranging from 1·02 (95% CI 1·01–1·04) to 1·10 (1·05–1·16).

See also:

It seems that long-acting CCBs (e.g. amlodipine), ARBs (e.g. telmisartan), and diuretics (e.g. indapamide SR) are best to control BPV. (While beta-blockers make it worse!)

Does this mean that you should add amlodipine @DeStrider? I don’t know. What’s your current telmisartan dose?

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