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Genetic Testing and Statin-related Muscle Side Effects
Genetic Testing and Statin-related Muscle Side Effects
Why Statins Are Prescribed
Statins (technically known as "HMG-CoA Reductase Inhibitors") are a class of medications that help manage cholesterol. They do so by lowering LDL cholesterol and triglycerides ("bad" types of cholesterol) and by modestly increasing HDL cholesterol (a protective form of cholesterol). As a result, build up and blockage of arteries by cholesterol particles is reduced.
But even beyond the direct effect on cholesterol build-up, statins have complementary
effects that provide benefit, like keeping cholesterol build-up in arteries stable so it is less likely to break-off and cause blockages in smaller blood vessels.
As a result of these effects, statins help to reduce the risk of serious health events, like
heart attacks and strokes due to blood clots.
SLCO1B1 and Other Gene Influence on Statin Muscle-Related Side Effects
Statins are generally well-tolerated by most people taking them. The benefits they provide tend to significantly outweigh negative aspects (i.e., statin side effects).
However, a modest number of individuals do experience muscle-related side effects (or statin induced myopathy). Symptoms may be described as pain, aches, cramps, and/or weakness, usually in larger muscles closer to the body (e.g., thighs) and tends to occur on both sides of the body. Some individuals find that they are worse after doing physical activities. These effects usually appear after weeks to months of starting a statin, or after dose increases. In some cases, some individuals will skip doses or stop the statin prematurely to reduce the impact of side effects on their quality of life. Since statins rely on consistent, as-prescribed use to prevent heart attacks and strokes, it is important to dive into this topic further.
Though these effects can be bothersome, they rarely cause any serious harm to the
body. Blood work related to the muscles usually is within a normal range.
It is important to note, however, that muscle-related symptoms can often be due to
many other causes, including injuries from exercise or physical work.
Sometimes, the expectation of experiencing muscle side effects from statins can also
create the perception of the side effect - this is known as a nocebo effect. For example, a friend or online search for "statin side effects muscle pain" may describe others' personal experiences with statins that influence our own expectations of taking the drug.
Otherwise, why do statins cause muscle pain?
Causes or contributing factors to muscle-related side effects from statins include
reduced functioning of someone's kidneys or liver. Low thyroid function can also play a role. Females and older individuals also have a higher risk.
Drug interactions can also play a notable role. For example, another cholesterol
medication called gemfibrozil, when taken with statins, may increase risk. Other drug
interactions are mostly specific to specific members of the statin class of medications,
including grapefruit/grapefruit juice.
Another very important factor is the specific statin used, and the dose selected. Some of the differences related to specific statins and doses relate to the biochemical processes that help determine how much of the statin makes it to the liver to reduce the body's production of cholesterol compared to how much stays in the blood and makes it to muscle tissues to cause side effects. These processes are often impacted by some of the factors discussed above but can also be impacted by genetics. For example, most statins can be impacted by a gene called "SLCO1B1". This gene programs a protein that allows these statins into liver cells. But in cases where its function is reduced due to specific gene variations in SLCO1B1, more statin than ideal can go to the muscle to cause bothersome pain. In the case of rosuvastatin, the gene ABCG2 also impacts how much medications makes it into the blood (alongside SLCO1B1). For fluvastatin, the metabolism gene CYP2C9 contributes to blood levels alongside SLCO1B1.
Genetic Testing for Atorvastatin vs Simvastatin Insight
Simvastatin is generally considered to be the most likely statin to cause muscle-related
pains, particularly at very high doses. So, if comparing, say, atorvastatin vs simvastatin,
we already have a sense of how risks of muscle-related side effects stack up. If you
have variations in SLCO1B1, the risk of muscle pain will be more significant with
simvastatin. Atorvastatin side effects (related to muscles) are less likely.
However, given the importance of statins in protecting the heart and brain from the
damages caused by build-up of cholesterol in the arteries, usually health care providers will start looking at other statins to try. One way to help them figure this out is by doing genetic testing for statin intolerance. This can help identify if you have variations in the specific genes discussed previously, and what this means in terms of risk and dose selection for each statin. It can also help your health care provider determine if certain statins might be worth avoiding. Having this information is ultimately about assisting your health care provider in considering genetic aspects of your clinical "picture" when providing care to you.
When to Consider Genetic Testing Before Starting a Statin
Genetic testing for statin medications can be done if you currently struggle with muscle pains while taking a statin, or if you have previously and decided to abandon use as a result. Not only could genetic testing help your health care provider determine if the symptoms are due to statins (e.g., SLCO1B1 variation statin myopathy) or otherwise, but it can also help select a specific statin and dose that is less likely to be problematic.
If can also help if you have yet to start a statin but are very concerned about muscle-
related side effects due to what a friend or family member has shared about their own
experience, or what you may have read or watched online. It can help ease your fears
and suggest specific approaches you can bring to your prescriber.
If you are currently on a statin but haven't tolerated trials of higher doses or more
potent alternative statins needed to help reach your health goals, genetic testing may
also help find a solution.
How Inagene Helps Personalize Cholesterol Treatment
Pharmacogenetic testing provides actionable insights that can support health care providers in their medication treatment decisions. The results help identify which medications or dosing strategies may be less likely to cause muscle-related side effects based on their genetic profile, allowing them to get the most out of their treatment.
