Thread by @sam_soete

𝗦𝘁𝗮𝘁𝗶𝗻𝘀 destroy your skeletal muscle, why would they be any good for your 𝗵𝗲𝗮𝗿𝘁?

This 🧵 dives deep into mechanisms underlying statin induced cardiomyopathy.

#statins #cardiomyopathy #CHF #heartfailure #health #bigpharma

Over 64 million people suffer from heart failure worldwide.

To what extent is statin therapy contributing to the epidemic of congestive heart failure (CHF) worldwide?

Statin cardiomyopathy is a complication that can occur in 1-3% of people.

M𝗶𝘁𝗼𝗰𝗵𝗼𝗻𝗱𝗿𝗶𝗮 are once again the linchpin linking statins to CHF.

Statins inhibit HMG-CoA reductase leading to a reduction in the bioavailability of prenyl-intermediates such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate, which synthesize Heme A and CoQ10 in the cholesterol biosynthetic pathway.

Oxidative stress borne out of 𝗖𝗼𝗤10 depletion can damage and mutate mtDNA, leading to inefficiencies in mitochondrial offspring.

I have already detailed in great depth how statins nuke our mitochondria here:

https://twitter.com/sam_soete/status/1657013095510966272?s=20

Statins decrease the concentration of mitochondria in skeletal muscle, OxPhos capacity, and skeletal muscle mtDNA levels.

It is not a big leap to think that statins would negatively impact cardiac myocytes that have an even greater metabolic demand.

Furthermore, statin-induced CoQ10 & Heme A depletion resulting in impaired cardiac contractility is associated with increased levels of 𝗯𝗿𝗮𝗶𝗻 𝗻𝗮𝘁𝗿𝗶𝘂𝗿𝗲𝘁𝗶𝗰 𝗽𝗲𝗽𝘁𝗶𝗱𝗲 (BNP).

BNP is a hormone that is produced and released by the ventricles of the heart in response to increased stretching or pressure on the cardiac walls.

Elevated levels of BNP serve as a biomarker for heart failure and can be used in its diagnosis, prognosis, and management.

Aside from CoQ10 depletion and subsequent mitochondrial destruction, statins can cause heart failure through another unique mechanism: 𝘀𝗲𝗹𝗲𝗻𝗼𝗽𝗿𝗼𝘁𝗲𝗶𝗻𝘀

Selenoproteins include 𝗴𝗹𝘂𝘁𝗮𝘁𝗵𝗶𝗼𝗻𝗲 𝗽𝗲𝗿𝗼𝘅𝗶𝗱𝗮𝘀𝗲, 𝗶𝗼𝗱𝗼𝘁𝗵𝘆𝗿𝗼𝗻𝗶𝗻𝗲 𝗱𝗲𝗶𝗼𝗱𝗶𝗻𝗮𝘀𝗲, 𝘁𝗵𝗶𝗼𝗿𝗲𝗱𝗼𝘅𝗶𝗻 𝗿𝗲𝗱𝘂𝗰𝘁𝗮𝘀𝗲, etc.

Glutathione peroxidase is an enzyme that plays a critical role in the antioxidant defence system.

It is involved in the detoxification of hydrogen peroxide and lipid hydroperoxides.

So how are statins and selenoproteins such as glutathion peroxidase connected?

Selenium is incorporated into selenoproteins through selenocysteinyl-tRNA (tRNAsc).

Similar to CoQ10 and Heme A, one of the bases of tRNAsc (isopentenyl adenine) is synthesized from a prenyl-intermediate.

Statin drugs deplete isoprenoid biosynthesis, including compounds like farnesyl pyrophosphate and geranylgeranyl pyrophosphate, by impairing the mevalonate pathway.

These isoprenoids play a crucial role in the post-translational prenylation of proteins.

The prenylation of glutathione peroxidase is important for its proper localization and function within the cell.

Prenylated glutathione peroxidase is typically anchored within cellular membranes, such as mitochondria, where it carries out its antioxidant activities.

The inhibition of glutathione peroxidase by statins increases peroxidative stress.

Statins also reduce levels of 𝘀𝘂𝗽𝗲𝗿𝗼𝘅𝗶𝗱𝗲 𝗱𝗶𝘀𝗺𝘂𝘁𝗮𝘀𝗲 𝗮𝗻𝗱 𝗰𝗮𝘁𝗮𝗹𝗮𝘀𝗲, which are antioxidants → ↑ oxidative stress.

Importantly, peroxidative stress causes atherosclerosis, carcinogenesis, and aging.

Glutathione peroxidase activity in erythrocytes is inversely correlated with CVD.

I explained in depth the mechanisms of how statins might cause CVD here:

https://twitter.com/sam_soete/status/1661732893989937152?s=20

How does this effect patients in real life?

Statins lead to the deterioration of patients with cardiomyopathy, but their condition can be salvaged if statin therapy is ceased in combination with CoQ10 supplementation.

It appears statin-induced cardiomyopathy is mainly a complication of long-term treatment.

In addition to the long-time horizon involved, few doctors are aware of the connection between statins and CHF, making it even more difficult to recognize in clinical practice.

Having just finished medical school, I can attest that this is not covered in any curriculum, and the side effects that are mentioned are limited to myalgia and largely disregarded.

Patients deserve better.

TLDR:

The depletion of:

• CoQ10
• Selenoproteins
• Heme A

play a role in statin-induced mitochondrial dysfunction and subsequent cardiomyopathy.

Thank you all for joining me in this rabbit hole.

What can you do to help me out?

1) If you could like and retweet the first tweet in this thread, I would really appreciate it.

2) Follow me if you want to see more informative content

#statins #heartfailure #health #CHF #CoQ10