Cardiovascular Health 2025

#971

It may be worthwhile to consider Taurine supplementation to lower hs CRP levels.
A systematic review and meta-analysis of controlled trials found that taurine supplementation significantly reduced hs-CRP

Profiling Inflammatory and Oxidative Stress Biomarkers Following Taurine Supplementation: A Systematic Review and Dose-Response Meta-Analysis of Controlled Trials.
Faghfouri AH, et al. European Journal of Clinical Nutrition. 2022;76(5):647-658.

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#972

I reviewed that paper and had GPT5 analyze it but there was no information on dose/response of Taurine’s influence on HS-CRP specifically. So I dug around more and found this information, from other papers:

Here’s what I could extract from the individual trials that actually report hs-CRP numerically, plus a simple pooled estimate.

Study-level hs-CRP changes with taurine

Population Dose & duration n (taurine) Baseline hs-CRP End hs-CRP Absolute Δ % Δ
Obese women (Rosa 2013/2014) 3 g/day × 8 wks 8 14.30 mg/L 10.50 mg/L −3.80 mg/L −26.6% (BioMed Central)
T2D (Moludi 2022) 1 g TID (3 g/day) × 8 wks (low-calorie diet in both arms) 60 3.17 mg/dL* 1.87 mg/dL* −1.29 mg/dL* −41.0%* (PMC)
T2D (Maleki 2020) 1 g TID (3 g/day) × 8 wks 26 — — — −16.01% (vs baseline) (BioMed Central)
Traumatic brain injury (Vahdat 2021) ~30 mg/kg/day (≤3 g/day) × 14 days 16 — — — ↓ within-group (p=0.02), group diff NS; medians shown only (no exact values) (PMC)
  • The Moludi paper prints hs-CRP in mg/dL; hs-CRP is typically reported in mg/L, so the unit label may be a misprint. The baseline→end values and change are as reported. (PMC)

Pooled estimates (from the trials with extractable numbers)

  • Pooled absolute change (weighted by taurine-arm n): −1.59 mg/L (Rosa + Moludi only). (BioMed Central)
  • Pooled percent change (weighted by taurine-arm n): −32.9% (Rosa + Moludi + Maleki). (BioMed Central)

Notes & caveats

  • Populations and co-interventions differ (obese women with counseling; two T2D cohorts, one on a hypocaloric diet; ICU TBI patients). Expect heterogeneity.
  • Two trials (Maleki 2020; Vahdat 2021) did not provide hs-CRP means/SDs in mg/L that could be extracted from the paper text/tables; Maleki reports only a −16.01% within-group reduction and significant between-group effect, and the TBI paper shows medians graphically (no extractable numbers). (BioMed Central)
  • I used simple n-weighted averages (not inverse-variance meta-analysis) because SDs of change weren’t consistently reported.
1 Like
#973

A paper from last year:

Anti-ageing interventions for the treatment of cardiovascular disease

In this review, we present the potential of emerging anti-ageing strategies, including epigenetic rejuvenation, metabolic reprogramming, autophagy activation, as well as senolytic and anti-inflammatory therapies, in delaying or reversing the development of age-related cardiovascular disorders, while considering potential sex differences. In doing so, we implicate cellular ageing processes in the pathogenesis of several prevalent cardiovascular diseases, such as atherosclerosis, hypertension, various types of cardiomyopathies (including its hypertrophic, ischaemic, dilated, diabetic, and arrhythmogenic forms) and heart failure, particularly that with preserved ejection fraction. Finally, we outline future challenges and steps needed for the implementation of these novel anti-ageing strategies in the clinical setting, with the aim of challenging the long-held notion of ageing as a ‘non-modifiable’ risk factor for cardiovascular diseases.

Open access paper:

https://academic.oup.com/cardiovascres/article/121/10/1524/7738987?login=false#530333049

Commentary on Rapamycin:

Rapamycin and its analogues effectively induce autophagy through mTORC1 inhibition,98 demonstrating cardiac benefits in aged female and male mice.99 Pharmacological inhibition of mTORC1 by rapamycin also extends lifespan across species.100 Interestingly, although this pro-longevity effect appears to be more pronounced in female mice compared to males,101,102 the cardioprotective actions of rapamycin are largely sex independent.99 Furthermore, even though rapamycin transiently activates autophagy,98 these anti-ageing benefits appear to be long-lasting.98,99 Rapamycin also confers vasoprotective effects in the form of reduced arterial stiffness, improved endothelial-dependent vasorelaxation and enhanced cerebral blood flow and attenuated atherosclerosis in relevant female and male animal models.103–105 Rapamycin also reduces hypertrophic cardiomyopathy, induced by aortic banding in rats (sex not reported).106 Rapamycin or its analogues attenuate advanced atherosclerosis,107 myocardial infarction and ischaemia-reperfusion injury in female and male rodents.108 However, these benefits were not translatable to humans, as shown in the CLEVER-ACS trial where mTORC1 inhibition using the rapalog everolimus failed to improve outcomes in patients with myocardial infarction.109 Rapamycin also has immunosuppressive actions and other off-target adverse effects, limiting its clinical cardiovascular utility.110

AI Summary and analysis:

Here’s a crisp, structured read of the paper you shared.

Summary (what the authors argue)

  • Thesis. Ageing is the dominant risk factor for CVD, yet no approved therapies directly target ageing mechanisms. The authors review emerging “anti-ageing” strategies—epigenetic rejuvenation, metabolic reprogramming, autophagy activation, anti-inflammatory pathways, and senolytics—as potential treatments or preventives for atherosclerosis, hypertension, cardiomyopathies (HCM, ICM, DCM, diabetic, arrhythmogenic) and especially HFpEF. They also emphasize sex differences in mechanisms and responses. (OUP Academic)
  • Scope. The review organizes cardiovascular ageing around cellular/hallmark biology and maps candidate interventions to cardiovascular phenotypes; the figures schematically link hallmarks to subclinical cardiac/vascular changes that set the stage for overt disease. (OUP Academic)
  • Translational stance. They highlight practical hurdles: lack of agreed biological-age endpoints, over-reliance on young rodents in preclinical CVD studies, and propose HFpEF and high-risk primary prevention as near-term clinical testing arenas. (OUP Academic)
  • Representative levers. Examples include HDAC modulation, DNA methylation modulators, miR-34a inhibition (epigenetics); NAD⁺/sirtuin pathways and other metabolic reprogrammers; autophagy inducers (including ACBPneutralization, spermidine), anti-inflammatory targets (e.g., NLRP3), and senolytics (e.g., D+Q/navitoclax class). They also note nutrients such as taurine showing multi-mechanistic effects (metabolic, anti-inflammatory, mitochondrial, and autophagic markers). (OUP Academic)
  • Context & provenance. Spotlight Issue on Ageing; accepted June 1, 2024; typeset Sept 4, 2024; appears in Cardiovascular Research Vol. 121(10):1524–1536 (Aug 2025). (OUP Academic)

What’s genuinely novel here

  1. Integrated, mechanisms-first clinical framing. Rather than listing compounds, the review threads shared ageing hallmarks to CVD phenotypes and intervention classes, then ties that to trial-design implications (e.g., endpoints, populations like HFpEF). That coupling of hallmarks → phenotype → trial strategy is unusually explicit for a cardiology review. (OUP Academic)
  2. Strong call-out of model age bias. The authors directly criticize the field’s dependence on young rodents for age-related CVD and urge ≥18-month mice to improve translation—a point often footnoted elsewhere but made central here. (OUP Academic)
  3. Positioning specific, less-discussed targets. Beyond usual suspects, they elevate ACBP neutralization, spermidine, and taurine as multi-modal levers with autophagy/mitochondrial angles in cardiovascular contexts. (OUP Academic)
  4. Operational guidance on endpoints & cohorts. They argue the real value may lie in primary prevention (residual risk) and propose HFpEF as a tractable starting disease model—useful, concrete guidance for trialists. (OUP Academic)

Critique (strengths & weaknesses)

Strengths

  • Clear mechanistic scaffold. Mapping ageing hallmarks to CVD phenotypes helps unify disparate geroscience data for cardiology audiences; the figures are didactic and actionable for hypothesis generation. (OUP Academic)
  • Translational realism. The paper is unusually candid about endpoint ambiguity, cost/length of trials for nutraceuticals/generics, and the sex-differences problem in both mechanisms and study design. (OUP Academic)
  • Constructive next steps. Suggesting HFpEF trials and enriched high-risk primary-prevention cohorts is practical and aligned with biology (fibrosis/stiffness, endothelial dysfunction, inflammageing). (OUP Academic)

Bottom line

A timely, mechanisms-first narrative that urges cardiology to treat ageing as a modifiable root cause. Its most valuable contributions are the translational framing (aged models, sex differences, HFpEF/primary prevention trial venues) and the cross-talk among pathways (autophagy–inflammation–metabolism). The enthusiasm is appropriate, but readers should weigh heterogenous evidence maturity, unresolved endpoints, and disclosed IP ties—especially around spermidine/ACBP—when prioritizing programs. (OUP Academic)

Citation note: Cardiocascular Research, Vol. 121(10):1524–1536; accepted June 1, 2024; published online Aug 22, 2024; Spotlight Issue on Ageing; conflict-of-interest disclosures as shown in the article. (OUP Academic)

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#974

So - I looked up this study that was referenced in the previous paper, and it seems far to short a study , for an acute situation, to conclude (as the previous paper did) that “these [many] benefits [of rapamycin use] were not translatable to humans, as shown in the CLEVER-ACS trial where mTORC1 inhibition using the rapalog everolimus failed to improve outcomes in patients with myocardial infarction.”

Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS) - A phase II, randomized, double-blind, multi-center, placebo-controlled trial

AI SUMMARY:

Here’s a structured summary, novelty identification, and critique of the uploaded paper:

:pushpin: Summary

Title: Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS) – A phase II randomized, double-blind, multi-center, placebo-controlled trial (American Heart Journal, 2022).

Background:

  • Acute myocardial infarction (AMI) triggers strong inflammatory responses that worsen infarct size and left ventricular (LV) remodeling.
  • Prior anti-inflammatory approaches (e.g., canakinumab in CANTOS, colchicine in COLCOT) have shown reduced cardiovascular events but mixed results for infarct size.
  • Everolimus, an mTOR inhibitor, has broad immunosuppressive effects on innate and adaptive immunity and reduces infarct size in preclinical models.

Objective:
To test whether a short 5-day course of oral everolimus after ST-elevation myocardial infarction (STEMI) treated with primary PCI can reduce infarct size, LV remodeling, and inflammation compared with placebo.

The CLEVER-ACS trial used a short 5-day oral regimen of everolimus:

  • Days 1–3: 7.5 mg once daily
  • Days 4–5: 5.0 mg once daily

So patients received a tapered schedule (7.5 → 5 mg qd), designed to give strong inhibition during the early inflammatory phase and then reduce dose to minimize risks of prolonged immunosuppression

:key: Novelty

  1. First RCT using systemic mTOR inhibition in acute STEMI: Previous uses of mTOR inhibitors were mainly in transplantation and stents; this is the first to test short-term systemic oral everolimus in the acute MI setting.
  2. Broad-spectrum immunomodulation approach: Unlike IL-1β or colchicine (targeted interventions), everolimus suppresses multiple immune pathways simultaneously, which may provide a stronger anti-inflammatory impact.
  3. Integration of advanced imaging and biomarkers: The trial uses serial cardiac MRI for precise infarct size quantification plus a biobank of inflammatory markers, offering mechanistic insight into immune modulation.
  4. Short, tapered regimen: A 5-day high-dose-to-lower-dose schedule is designed to capture early inflammation but minimize prolonged immunosuppression.
  5. Bridging preclinical and human translation: Builds directly on animal data showing infarct size reduction with mTOR inhibition.

:face_with_monocle: Critique

Strengths:

  • Rigorous design: Phase II, randomized, placebo-controlled, double-blind, multi-center with independent DSMB and adjudication.
  • State-of-the-art endpoint: Use of cardiac MRI, gold standard for infarct size and LV remodeling.
  • Mechanistic depth: Biomarker profiling and immune cell analysis increase translational value beyond clinical outcomes.
  • Practical dosing: The short regimen reduces risks associated with long-term immunosuppression.

Limitations / Concerns:

  1. Timing of intervention:

    • Everolimus is oral only; initiation is delayed (up to 5 days after reperfusion).
    • The most intense inflammatory phase occurs within the first 24–72 hours post-MI; late administration may miss this critical window.

  2. Sample size & power:

    • n=150 is modest and powered for infarct size change, not clinical outcomes.
    • May be underpowered to detect subtle effects or safety signals.

  3. Short follow-up (30 days):

    • Remodeling and heart failure development often evolve over months.
    • The design does not assess medium/long-term functional or clinical benefits.

  4. Safety considerations:

    • Even short mTOR inhibition may impair wound healing, infection defense, or cause cytopenias, especially in acutely ill patients.
    • Immunosuppression in STEMI patients could have unforeseen risks (though prior sirolimus/everolimus trials in PCI show low side effects).

  5. Comparator limitations:

    • The placebo-controlled design is appropriate, but comparison to other anti-inflammatories (colchicine, IL-1 inhibitors) could provide more context on relative benefit.

:dart: Overall Assessment

The CLEVER-ACS trial is an innovative and ambitious translational study, testing whether short-course systemic mTOR inhibition can reduce infarct size in STEMI patients. Its novelty lies in the broad-spectrum immunomodulatory approach, robust imaging endpoints, and translational biomarker work.

However, it faces practical limitations: modest sample size, late start of therapy relative to peak inflammation, and short follow-up. Even if positive, the findings would primarily justify a larger phase III trial rather than changing clinical practice.

Interpretation & Implications

Given the negative (null) primary and key secondary results, here are some considerations and caveats:

  1. Lack of efficacy vs negative result
  • The trial failed to demonstrate a benefit of everolimus in reducing infarct size or MVO in this clinical setting.
  • This suggests that either the hypothesis (that mTOR inhibition mitigates post-MI inflammation in a meaningful way) was incorrect, or that aspects of trial design (timing, dose, patient selection) limited the ability to detect an effect.
  1. Window of inflammation & timing
  • Much of the injurious inflammatory cascade post-MI occurs very early (hours to 1–2 days). Because the intervention began within up to 5 days post-PCI, it may have missed the optimal therapeutic window.
  • Even though “baseline” CMR was defined between 12 h and 5 days post-PCI, the modulation of inflammation may have been too late to alter infarct evolution.
  1. Dose, duration, and tissue penetration
  • It’s possible the used dose and duration were insufficient to meaningfully suppress relevant inflammatory pathways in the myocardium (or in recruited leukocytes) without causing unacceptable systemic immunosuppression.
  • Tissue-level drug delivery in infarcted myocardium, where perfusion is compromised, might have been suboptimal.
3 Likes
#975

The study of the lady who died aged 117 had her (LDL-C) cholesterol results in the supplementary data. They were a bit high, but I don’t remember the US conversion ratio for this biomarker and to be fair they should have been measured over a number of years to have any significance.

My own personal CRP is hyperlow normally, Lp(a) quite low or immeasurably low, ApoB at bit iffy and LDL-C goes over and under the UK action threshold of 3. Hence I have not been taking a statin although I do take a lot of pantethine when drinking.

2 Likes
#976

On colchicine:

This trial failed: Colchicine in Acute Myocardial Infarction 2024

image
image1168×1386 198 KB

However:

image
image1176×302 63.8 KB

So I’m still not convinced regarding colchicine…

3 Likes
#977

This is a very interesting point, but I disagree with the AI here. What is known (I work in pretty much this field) is that acute inflammation after MI is not necessarily a bad thing. If you completely remove inflammation in the early phase, you actually end up with worse repair in the long run. That’s because the acute response is what recruits macrophages to clean up damage, releases cytokines to stimulate new vessel formation etc. So I think the study approach of dosing 5 days post-MI makes complete sense.

The real question is whether the study ran for long enough. Also, IMO, infarct size is probably not the most suitable measurement, since that is usually determined by the duration of ischaemia and how quickly the coronary artery was re-opened. Looking at longer-term cardiac function would have been better, but like always they were probably limited by resources and money.

ApoB/LDL-C/Lp(a) is necessary for ASCVD, but it’s not sufficient all by itself. Some people are just lucky and they go their whole life with high ApoB/Lp(a) and never build plaque, and others are unlucky and build plaque at 60mg/dl ApoB. The bigger picture is that lipoproteins enter the artery wall by complex mechanisms, and they can flux in and out. Some people can seemingly efflux particles quite well, while others don’t. But the total ApoB is absolutely super important because it’s the building block of the plaque. The inflammation, artery wall damage (hypertension etc), oxidative stress etc are what accelerates the process.

So I think while it’s great to have low hsCRP and Lp(a), I would still address my “iffy” ApoB, unless you have really good reasons not to.

Thanks for sharing the two posts.

The first screenshot relates to secondary prevention in people who’ve already had MI. So I do agree with Tom Dayspring here that using the drug to lower inflammation in stable chronic CAD is completely different. I reckon the new ACC Scientific Statement has it right; you consider the drug if you have persistent high hsCRP that won’t go down with statins, exercise, diet etc. Which reminds me, I need to check my own hsCRP now that I’ve been on Rapa for ~6 months, hehe

3 Likes
#978

Is rapa known to increase hsCRP?

#979

Wouldn’t you expect the opposite? Rapa lowering inflammatory biomarkers? I have not observed this in myself after a few months of rapamycin 6mg/1-week, my hsCRP is within the same range as before (0.25 - 0.5). I have not measured my IL-6, so I don’t have a baseline, although I intend to test for this early next year.

1 Like
#980

Not expecting anything, just curious.

#981

I have CRP values each week. The minimum level on one lab is 0.3 and the other 0.15. Norrmally my CRP is below the minimum threshold although sometimes (as a result of temporary infection) it is higher. Looking at the results and given that the frequency at which I take rapamycin is every 6 weeks or less frequently I don’t see any effects.

1 Like
#982

I’m expecting it to be lower :slight_smile:

1 Like
#983

Nick Norwitz our lovable mischief maker has another curveball interview with noted skeptic cardiologist Bret Scher. They get into the PCSK9i and Alzheimer Disease MR study, statins and GLP-1RA and other areas.

I Interrogate a Cardiologist | Dr. Bret Scher on Cholesterol, Heart Disease & Alzheimer’s (Nick Norwitz)

2 Likes
#984

When I was taking rapamycin daily (1mg daily 2 weeks, 1 week off), my hsCRP went down from 0.3 to 0.15. Unfortunately, I don’t have weekly tests to track it closely, but at the time I was doing monthly labs and the decrease seemed pretty stable.

Now that I’ve paused rapamycin, my hsCRP usually sits between 0.2 and 0.3 again. Very small fluctuations, probably insignificant and maybe hard to say it was just rapamycin.

3 Likes
#985

Why did you pause Rapa after 1mg/2 weeks - 1 week off?

#986

@relaxedmeatball
I looked up labs when crp was tested…

HS CRP .7 03/2018

CRP .8 07/2018
does not say it was HS, so I’m calling it out incase it makes a difference).

HS CRP 1.0. 01/2022

HS CRP .9 07/2022

CRP (not HS). 1.3 12/2022

HS CRP .90 03/2023

Started colchicine summer of 2023

Started rapa spring of 2024

CRP ‘cardiac’ .7 07/2024

CRP ‘cardiac’ .75 02/2025

PS
@RapAdmin, or everyone,
did anyone wind up finding a good program to keep track of our labs?

4 Likes
#987

Clinical Trial Overview

  • A new clinical trial investigated the effects of exercise on artery plaque in patients with significant plaque buildup and angina, all of whom were on lipid-lowering treatments.
  • Participants were randomly divided into two groups: a control group that received standard care advice and an intervention group that participated in a supervised high-intensity interval training (HIIT) program.
  • The control group followed guidelines that included a healthy diet, smoking cessation, regular exercise, and management of blood pressure and glycated hemoglobin levels.
  • The intervention group engaged in a structured HIIT program, which included treadmill or stationary bike workouts with specific heart rate targets.

HIIT Program Details

  • The HIIT program consisted of a 10-minute warm-up at 60 to 70% peak heart rate followed by cycles of high-intensity and recovery periods.
  • Each cycle included 4 minutes at 85 to 95% peak heart rate followed by 3 minutes at 60 to 70% peak heart rate, repeated four times, and concluded with a 5-minute cooldown.
  • Participants completed this workout twice a week under professional supervision and were encouraged to perform additional HIIT exercises at home.

Results of the Study

  • After six months, the study measured the plaque size in arteries, revealing no significant changes in the control group, while the HIIT group showed a notable reduction in plaque size.
  • The largest lesion in the HIIT group reduced from an average of 49.5% of the artery lumen to 48.3%, indicating a 1.2% decrease in plaque size.
  • This 1.2% reduction in plaque size is significant, as similar reductions in other studies have correlated with a 20 to 25% decrease in the risk of cardiovascular events.

Understanding Plaque Composition

  • While plaque size reduction is important, the composition and structure of the plaque are critical factors that influence its stability and risk of rupture.
  • Plaque can become more stable without necessarily shrinking, which means it could even increase in size while becoming less dangerous.
  • Further research is needed to explore how different types of exercise, such as cardio versus weight training, affect plaque dynamics and overall cardiovascular outcomes.

Mechanisms Behind Plaque Reduction

  • The HIIT group also exhibited significant reductions in body mass index (BMI) and waist circumference, suggesting that weight loss may contribute to the decrease in plaque size.
  • Interestingly, there were no significant changes in hemoglobin A1c, LDL cholesterol, or APOB levels between the HIIT group and the control group, which is noteworthy given the established role of lipid-lowering treatments in reducing plaque.
  • All participants were on lipid-lowering treatments, maintaining their LDL cholesterol around 80 mg/dL, a level known to halt plaque growth.

Implications for Future Research

  • The study raises questions about the potential additive effects of combining exercise with lipid-lowering therapies to achieve more significant plaque regression.
  • Future research is needed to determine if lower lipid levels combined with exercise could lead to faster plaque reduction or if both interventions operate through similar mechanisms.
  • Understanding these dynamics is crucial for developing effective treatment strategies for patients with cardiovascular disease.

Conclusion and Further Resources

  • The results of this trial are encouraging, indicating that HIIT may play a beneficial role in managing arterial plaque among high-risk patients.
  • For additional insights on lowering APOB through lifestyle changes and effective workouts to reduce blood pressure, viewers are encouraged to explore related video content.

Note: Dear all: Just a quick clarification regarding the “peak heart rate” mentioned in the video. Multiple viewers asked if several minutes at 85-95% “peak heart rate” isn´t too strenuous, especially for patients with heart disease.

Although the study Methods aren’t entirely clear, it seems they performed a ramp test prior to the study to determine each participant´s exertion limit. This test started at a comfortable intensity, which was gradually increased every minute until the participant stopped due to exertion (or until VO2max was achieved).

It seems, then, that “peak HR” refers to the highest HR recorded during this test before the participant chose to stop it.

In HIIT, it is customary to calculate “maxHR” by subtracting age from 220. It appears “peak HR” used in this study is unrelated to this calculation, and is instead a personalized measure obtained empirically. In other words, two participants with the same age could have wildly different “peak HRs” depending on their condition. This allowed them to tailor the exercise to each person’s ability and tolerance.

Finally, the main takeaway from this study is that physical activity has the potential to deliver some plaque regression. The specifics (type and exact protocol used) may or may not be important (more work will be required to establish this).

Hope this makes sense and thanks to the attentive viewers for the inquisitiveness of bringing this to our attention.

Gil

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#988

I followed this schedule for about a year, but I recently paused rapamycin. I had minor surgery that damaged my glossopharyngeal nerve, and I was afraid that taking rapamycin would hinder the regenerative capacity. I plan to resume rapamycin by the end of the year, following the same schedule.

2 Likes
#989

Beth, I am using this app, Carrot Care. It seems good. I use the free version, and I need to input my labs manually. But if I remember correctly, you can take a photo or upload external labs with the paid version. You can set reminders, etc. I am not saying it is flawless, but it does the work.

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#990

Thanks so much for sharing Beth! So it overall didn’t change much, but it’s nice and low and stable, which is awesome!

1 Like