Statins and Cholesterol
28
August

By Adem Lewis / in , , , , , , , , , , , , , , , /


Of all the known diseases, heart attacks are
the leading cause of death worldwide, with strokes coming a close second. Both are considered types of cardiovascular
disease. Due to their prevalence and lethality, treating
and preventing cardiovascular diseases is a huge priority in our healthcare system. If you are at risk of having a heart attack
or stroke, doctors will likely prescribe you a class of drugs called statins, which decreases
LDL cholesterol levels. So what is LDL cholesterol, how do statins
decrease LDL cholesterol, and why does that decrease the risk of cardiovascular disease? Learn more about how statins work, who should
take them, and what the side effects are in this episode of Medicurio. In humans, cholesterol is an essential molecule
used to make steroid hormones, bile acids, and Vitamin D. It is also a vital part of the cell membrane
of each and every cell in the body. Most of the cholesterol in our body is synthesized
in the liver and transported to other parts of the body via blood. However, cholesterol is insoluble in blood
and must be packaged within special particles called low-density lipoprotein particles to
enter the blood. When cholesterol is within these particles,
it is referred to as LDL-cholesterol. There is generally less than 100 mg/dL of
LDL-cholesterol flowing through the blood of a healthy adult. When the blood vessel wall is damaged due
to high blood pressure, increased fats and cholesterol in blood, high blood sugar from
diabetes, or toxins from smoking, a complex inflammatory response occurs in which plaque
begins to form at the site of damage. Plaque is a buildup of LDL cholesterol, other
fats, and dead immune cells, covered by a cap of smooth muscle cells. What makes plaque so dangerous is that the
cap can rupture, revealing the interior of the plaque which can trigger blood clot formation
and blood vessel blockage. A heart attack occurs when blood vessels within
the heart become blocked by this process. Heart tissue supplied by those blood vessels
become deprived of nutrients and oxygen and eventually die. The heart no longer pumps properly, fatally
shutting down the body. The same blockage could happen in the blood
vessels of the brain to cause strokes, leading to brain damage and possibly death. Considering that LDL cholesterol is one of
the main components of plaque, it is not surprising that many studies have linked higher LDL cholesterol
levels to a higher risk of cardiovascular disease. This prompted scientists to look for drugs
that decrease LDL cholesterol levels to prevent cardiovascular disease. In 1971, biochemist Dr. Akira Endo and his
team isolated the first statin, compactin, from the fungus Penicillium. Based on compactin’s early success in lowering
LDL cholesterol, pharmaceutical companies began creating structurally similar molecules
with different potencies and rates of breakdown, giving patients a wide range of statins to
choose from that will best benefit their individual situations. The effectiveness of statins have made them
one of the most highly prescribed and commercially successful drugs in the world, with the most
popular statin, atorvastatin, raking in over $125 billion dollars worldwide since its creation
in 1996. So why are statins so effective at loweromg
LDL cholesterol? To understand how statins work, we first need
to understand how cholesterol is made in the body. The cholesterol synthesis pathway involves
multiple steps. The most important step of the entire pathway
is the formation of mevalonate from a molecule called HMG-CoA. HMG CoA contains Coenzyme A, which is removed
to form mevalonate. This reaction is carried out by an enzyme
called HMG-CoA reductase. It turns out that statins can also bind to
this enzyme because statins and HMG-CoA have similar structures. However, HMG-CoA cannot bind to the enzyme
if a statin is occupying that binding site, meaning that no reaction occurs and no mevalonate
can be formed. This is how statins stop cholesterol synthesis. So how does stopping cholesterol synthesis
using statins affect LDL cholesterol levels in the blood? Without cholesterol synthesis, the liver now
needs to look for other sources of cholesterol to create bile and other important compounds. The only major source of cholesterol left
now is in the blood, packaged as LDL cholesterol. To reabsorb the LDL cholesterol, liver cells
begin to express LDL receptors on their surface, which bind to LDL particles, internalizes
them, and breaks them down to obtain cholesterol. This removes LDL cholesterol from the blood,
resulting in lower LDL cholesterol levels and a lower risk of developing plaque and
cardiovascular disease. So who should take statins and what are some
possible side effects? Statins should be taken by people who are
at a high risk of developing cardiovascular disease. Though guidelines vary between healthcare
systems, generally this includes people who have very high LDL cholesterol levels above
190 mg/dL, are living with diabetes, have a family history of cardiovascular disease,
or have already had a heart attack, angina, or stroke. Essentially, any conditions that may cause
plaque to form. As for side effects of statins, around 5 to
10% of statin users experience clinically significant muscle pain and weakness, which
understandably causes some of them to stop taking their medication. Although stopping stain use may relieve muscle
pain, high-risk patients lose the preventative effects of statins, possibly resulting in
a lethal heart attack or stroke. Instead, patients should discuss their pain
with their doctor and perhaps switch to other cholesterol-lowering drugs or undergo lifestyle
changes, but once again, do not simply stop taking statins without an alternative method
of decreasing LDL cholesterol. Unfortunately, the mechanism of muscle damage
by statins is not well understood. One possible explanation is that molecules
produced in the cholesterol synthesis pathway are also used to synthesize a molecule called
CoQ10. CoQ10 is involved in cellular energy production, particularly at energy-consuming tissues such as muscles. Inhibiting HMG-CoA reductase by statins may
also be causing a decreased synthesis of CoQ10, which might impair energy production in muscle
to cause muscle pain and weakness. Aside from this, statins are a relatively
safe drug to use with proper dosage. There is no question that statins can reduce
LDL cholesterol levels as intended, and has likely prevented countless heart attacks,
strokes, and deaths worldwide. However, the fact that statins are one of
the most prescribed drug classes points to an underlying problem in lifestyle choices
that have made cardiovascular disease so common. As a society, we should move towards becoming
healthy enough to avoid statin use. Thanks for watching, and see you next time
on Medicurio.


49 thoughts on “Statins and Cholesterol

  1. This is a reupload, I mistakenly said "decalitres" instead of "decilitres" when discussing LDL cholesterol levels in the previous upload (thank you John B for pointing that out). Apologies for any confusion.

  2. Got sent here by TierZoo, and fell in love with this channel, have already watched every video. I especially like how you use visuals to help explain different concepts. Keep up the good work!

  3. The animations are great, you can get better at talking, but I think you should pick more interesting topics if you want to be an enterntainer.

  4. "…Or undergo lifestyle changes."

    Lmao yeah, I eats a ton and I'm fat. But its okay, I got the pills, unless they don't works either.

  5. Came here from tierzoo, by the time I saw his shoutout to your channel, I insta-clicked your channel to check it out. Your channel has the potential to become the best medicine oriented channel here in youtube. So keep uploading 😀

    Also a video about ABCs (Acute biologic crisis) would be great. 🙂

  6. Go vegan! My doc wanted to put me on stains without even suggesting a diet adjustment. Make sure you look at your diet first

  7. Losartan, Lisinopril, Atorvastatin (sometimes Simvastatin) and then Insulin, Glipizide, and Metformin. I work in a pharmacy and I sell bag after bag after bag filled with bottles of these meds for patients every day. I'm really stoked to have found this channel because the format in which you create your vids helps me grasp what the heck I'm actually doing every day. It's interesting!!!

  8. Great video, I think everyone should atleast taste SOME statins since we like in a world of junk food and bad habits. Maby not 1 a day. Maby atleast 1 a week. To stay on the safe side ya know. Btw, love your channel. Keep uploading. Topic: how cancer grows.

  9. Many doctors automatically default to prescribing statins, at least my former doctor did. This may also be a reason so many statins are prescribed.

  10. @03:57 you claim that statins are effective in lowering LDL, but there is no quantitative information on it in the video either before that point or after.

  11. Nicely done 👍.

    Personally, I would never take a statin, but I think this is a well done, simplified explaination of how they work.

    I especially like the fact that just enough background chemistry is shown to illustrate its mechanism of action along with a brief mention that it "may" interfere with CoQ10 metabolism (though I think this is more of a "definitely" than a "maybe.")

  12. 70mg/dl ldl and below all the way baby!!! This need for guideline change is long overdue.

    Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. – 50% of heart attacks happened in patients with "safe" cholesterol levels (out of 232k people), below 100 mg/dl ldl. Guideline
    "optimal" levels are below 100 mg/dl cholesterol and "near optimal" are 100 – 130 mg/dl. Doctors will sometimes say near optimal levels are not to be worried about.

    Normal LDL-Cholesterol Levels Are Associated With Subclinical Atherosclerosis in the Absence of Risk Factors. – 1800 healthy subjects studied (non smokers, no hypertension, diabetes, or dyslipidemia and so on). Those subjects were considered CVRF (cardiovascular risk factor) free. 50% of those "risk free" participants had clear plaque or coronary artery calcification present. This can be seen by vascular ultrasound and cardiac computed tomography. This once again found that an ldl of 50 – 70 mg/dl is where atherosclerosis does not exist. Meaning we need to make the safe optimal guideline levels of ldl even lower.

    Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. – Atherosclerosis wasn't seen in people with a 50 – 70 mg/dl ldl. Lowering LDL also reduced inflammation and improved endothelial function.

    PCSK9 gene mutations and low-density lipoprotein cholesterol. – A loss-of-function gene mutation "PCSK9" that reduces mammal/human ldl levels greatly reduced CHD events. Mutations in a specific gene located on chromosome 1 causes low levels of PCSK9 and low levels of PCSK9 will lead to less breakdown of LDL-receptors causing people to have very low levels of LDL. If you produce less of this protein more cholesterol goes out of your bloodstream meaning you have a lower serum cholesterol.

    Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. – 3.35k black subjects studied. 2.6% (87 people) were loss-of-function gene mutation PCSK9 carriers. Those carriers had 28% reduction in mean ldl and an 88% reduction in risk of CHD. 9.5k white subjects studied. 3.2% (304 people) were loss-of-function gene mutation PCSK9 carriers. Those carriers had a 15% reduction in mean ldl and a 47% reduction in risk of CHD. Despite having the exact same diet as the control group (SAD diet/lifestyle).

    Relation between progression and regression of atherosclerotic left main coronary artery disease and serum cholesterol levels as assessed with serial long-term (> or =12 months) follow-up intravascular ultrasound. – 60 white patients studied. Tested by IVUS (serial intravascular ultrasound) once at the beginning and then one year later. Split into 2 groups. Qualifiers for group A = more than 120mg/dl ldl = 26 patients. Qualifiers for group B = less than 120mg/dl ldl = 34 patients. Both groups had similar medication use except more statin use in group B. Group A's total mean cholesterol was 219 mg/dl, ldl 158 mg/dl, hdl 42 mg/dl, triglycerides 114 mg/dl. Group B's total mean cholesterol was 173 mg/dl, ldl 89 mg/dl, hdl 51 mg/dl, triglycerides 144 mg/dl. Group A plaques showed more P&M (plaque plus media, basically atherosclerosis) progression than group B plaques (24/26 [92%] versus 17/34 [50%]) and tended to have a greater frequency of lumen reduction (more blockages/atherosclerosis, less blood flow) (17/26 [65%] versus 15/34 [44%]). Once again, this found that an LDL value of 75 mg/dL is the cutoff at which atherosclerosis does not progress. The higher your ldl the faster your progression of atherosclerosis.

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