Not sure how much (if at all) tirzepatide would affect cardiac remodeling in a lean, hypermuscular bodybuilder on steroids.
Evidence that tirzepatide protects against diabetes-related cardiac damages: āOur findings indicate that TZT has beneficial effects on cardiac cells by positively modulating cardiomyocyte death, fibrosis, and hypertrophy in the presence of high glucose concentrations. This suggests that TZT may reduce the risk of diabetes-related cardiac damage, highlighting its potential as a therapeutic option for heart failure management clinical trials. Our study strongly supports the rationale behind the clinical trials currently underway, the results of which will be further investigated to gain insights into the cardiovascular safety and efficacy of TZT.ā
Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure: SUMMIT CMR Substudy: āThe CMR substudy of the SUMMIT trial demonstrated that tirzepatide therapy in obesity-related HFpEF led to reduced LV mass and paracardiac adipose tissue as compared with placebo, and the change in LV mass paralleled weight loss. These physiologic changes may contribute to the reduction in heart failure events seen in the main SUMMIT trial. (A Study of Tirzepatide [LY3298176] in Participants With Heart Failure With Preserved Ejection Fraction [HFpEF] and Obesity: The SUMMIT Trialā
Tirzepatide attenuates lipopolysaccharide-induced left ventricular remodeling and dysfunction by inhibiting the TLR4/NF-kB/NLRP3 pathway: āIn brief, tirzepatide attenuates LPS-induced left ventricular remodeling and dysfunction by inhibiting the TLR4/NF-kB/NLRP3 pathway.ā
Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial: āTirzepatide reduced cardiac injury, reflected by decreases in troponin T, and reduced wall stress, reflected by decreases in NT-proBNPā
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The fact that it paralleled weight loss suggests it was the weight loss rather than a direct mechanism. The other potential mechanisms are interesting, so weāll see if they pan out. I think the evidence for ARBs and SGLT2i drugs is much better established and is independent of weight loss (thus more likely to be useful in a lean person).
A lot of people like to claim GLP1s main mechanism of effects other than weight loss are due to the benefits of weight loss but there are receptors for GLP1 in many areas of the body.
Of course I want to see more data, but I have a good feeling about them, particularly tirzepatide.
Yes however there has been serious doubt cast in recent years that an isolated high RBC, hematocrit, and hemoglobin itself increases risk of any thrombotic or cardiovascular events, unless platelets are also elevated. Since steroids do not increase platelet counts, this doesnāt appear to be anything major to worry about, despite seeing them flagged as HIGH on a lab test.
Itās similar to people living at very high altitudes walking around with hematocrits of 60 most of their lives. They have no increased risk despite such high numbers.
I took an echocardiogram about 5 weeks after starting retatrutide and noticed my left atrium measured a bit smaller than previous years. Could just be a simple measurement difference from technician to technician or maybe there is something more to it
Here is a mouse study on this
Glucagon-Like Peptide-1 Protects Against Atrial Fibrillation and Atrial Remodeling in Type 2 Diabetic Mice - PMC.
And a human one with combo therapy
Effects of Liraglutide, Empagliflozin and Their Combination on Left Atrial Strain and Arterial Function - PMC.
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Iāve seen some recent claims about this (maybe on YouTube?), but a quick search reveals a couple of recent studies suggesting the rise in hematocrit from T therapy is an independent risk factor for MACE:
This is from OpenEvidence:
"Elevated hematocrit from testosterone therapy is independently associated with increased risk of major adverse cardiovascular events (MACE), regardless of whether platelet counts are elevated. The medical literature and clinical guidelines focus on hematocrit thresholds (typically ā„52ā54%) as the primary risk factor for MACE and venous thromboembolism in this context, not on the presence of concomitant thrombocytosis. The pathophysiology is thought to be related to increased blood viscosity and hypercoagulability from erythrocytosis, which can promote thrombosis and impair microvascular perfusion, even in the absence of elevated platelet counts. [1][2][3][4]
No evidence or guideline from the Endocrine Society or recent cohort studies suggests that the risk of MACE is mitigated if platelet counts remain normal when hematocrit is elevated; clinical recommendations focus on monitoring and managing hematocrit alone.[2][3][4] While the interaction between hematocrit and platelet count has not been specifically studied in large cohorts, and a modifying effect of platelet count cannot be fully excluded, the current consensus is that elevated hematocrit itself is sufficient to increase cardiovascular risk in men receiving testosterone therapy.[1][2][3][4]
Therefore, the risk of MACE persists with elevated hematocrit, even in the absence of thrombocytosis, and clinical management should be guided by hematocrit levels alone."
References
- Secondary Polycythemia in Men Receiving Testosterone Therapy Increases Risk of Major Adverse Cardiovascular Events and Venous Thromboembolism in the First Year of Therapy. Ory J, Nackeeran S, Balaji NC, Hare JM, Ramasamy AR. The Journal of Urology. 2022;207(6):1295-1301. doi:10.1097/JU.0000000000002437.
- Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. Bhasin S, Brito JP, Cunningham GR, et al. The Journal of Clinical Endocrinology and Metabolism. 2018;103(5):1715-1744. doi:10.1210/jc.2018-00229.
- Rises in Hematocrit Are Associated With an Increased Risk of Major Adverse Cardiovascular Events in Men Starting Testosterone Therapy: A Retrospective Cohort Claims Database Analysis. Kohn TP, Agrawal P, Ory J, Hare JM, Ramasamy R. The Journal of Urology. 2024;211(2):285-293. doi:10.1097/JU.0000000000003786.
- Haematological Actions of Androgens. Warren AM, Grossmann M. Best Practice & Research. Clinical Endocrinology & Metabolism. 2022;36(5):101653. doi:10.1016/j.beem.2022.101653.
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Iām glad you shared there.
Reading the second study, I am seeing the risk of MACE is 5.15% in high hemarocrit group compared to 3.86% for people with normal hematocrit. That is higher but not by much if you ask me.
Itās definitely really interesting, but I have to suspect that people living at high altitudes also have a lot of other systemic changes (lung efficiency, microvessel density etc) which wouldnāt be the case with drug use (testosterone, EPO etc). I also think thereās a line to draw between TRT within physiological ranges, and the doses used by bodybuilders.
I am seeing the risk of MACE is 5.15% in high hemarocrit group compared to 3.86% for people with normal hematocrit. That is higher but not by much if you ask me.
I havenāt checked the paper, but if those are absolute risk numbers, they would be a >30% increased risk? Thatās not nothing IMO.
Iām not saying theyāre the same but in both cases, the platelets are not elevated, which is why I made the comparison.
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