Nutrition

Statins To Lower Bad Cholesterols: Who Needs It And Who Is Better Off Without It

For the general healthy population, a healthy lifestyle alone is sufficient. In some cases, however, statins can save lives.

Statins save lives, and most experts will agree. Because it helps reduce the risk of getting heart diseases that have, so far, taken almost 18 million lives away. And it does so by lowering the LDL or “bad” cholesterol levels. However, as with any other drug, statins come with side effects — one of the main reasons that drove many statin users to ditch them.

At a glance, the lack of exposure to the additional risks of side effects seems beneficial. After all, cholesterol levels can generally be controlled mainly through a healthy diet and other lifestyles.

At least, this holds true for people with a low or moderate risk of developing heart diseases. For people with high risks, however, ditching statins could mean giving up the forest for the trees.

Before we judge whether statins are worth taking, let’s first understand what LDL cholesterols are and how statins work so that we don’t take or get rid of them for the wrong reasons.

Fats And Cholesterols

Fats and cholesterols are a type of lipids. They are generally needed by our cells to make energy and important components like steroid hormones, vitamin D, bile acid, or cell structures.

These supplies can be obtained through diet or made by the liver through a process called de novo [newly] synthesis.

• In terms of diet, fats from food are gradually broken down into smaller molecules and then processed into triglycerides (TG) — the main constituent of natural fats and oils — in the small intestines. Here, the TG and cholesterols are transported to places where they are needed — such as the muscle cells and cardiac muscle cells to be used for energy, or the adipose cells to be stored.
• In terms of de novo synthesis, TG and cholesterols are synthesized in the liver using pre-existing components stored in the adipose [fat] cells. Then, they are transported directly to the cells.

But because TG and some cholesterols are insoluble in water (just like how it looks when you mix oil and water), they need to be packaged into molecules called lipoproteins. This allows them to travel to the cells via the bloodstream.

Lipoproteins

Lipoproteins are spherical molecules that are amphipathic. That is, they have a water-binding surface and a lipid-binding core made of TG, cholesterol, phospholipids, and proteins (e.g., apoprotein B, ApoB).

And depending on their constituents, they are categorized into four main types:

• Chylomicrons: The largest lipoproteins. Consists of the highest and lowest composition of TG (~90%) and cholesterol (~5%), respectively. Serves to transport TG and cholesterols from the small intestine to the cells when supplies are obtained from the diet.
• Very low-density lipoprotein (VLDL): The second-largest lipoproteins. Consists of ~60% TG and ~20% cholesterol. Shuttles TG and cholesterols from the liver to the cells when supplies are obtained from de novo synthesis.
• Low-density lipoprotein (LDL): Third largest lipoprotein. Consists of a low TG (~8%) but is richest in cholesterol (~50%). A by-product of VLDL as most of the TGs are removed from it, leaving it with mainly cholesterols.
• High-density lipoprotein (HDL): Smallest lipoproteins with ~5% TG and ~25% cholesterol. Involved in reverse cholesterol transport and is known as the “good” cholesterol.

So, the LDL or “bad” cholesterol that people often refer to is actually a lipid-delivering molecule. But why are they harmful?

It’s In The Numbers

Essentially, LDLs circulate in the blood while certain enzymes extract the cholesterols from it to give to the cells. When the LDLs reach the liver, they bind to the LDL-receptors present on the surface of the liver cells. Then, they enter the cells and get broken down. This clears off the LDLs from the bloodstream.

However, circulating LDLs may sometimes get hooked up to the walls of the arteries and squeeze themselves into the inner linings. Within the walls of the artery, the LDLs may oxidize, a reaction that increases its tendency to react with the surrounding tissues or molecules.

This causes an immune response where macrophages — immune cells that serve to clear off unwanted substances in the body — travel to the specific site to pick up and eliminate these oxidized LDLs.

Usually, this doesn’t lead to any complications. However, if this happens too frequently, the macrophages will take up so many cholesterols that they become loaded with them. This can make them secrete substances that contribute to plaque formation, or the macrophages might die, and their remains will form the core of the plaque.

Hence, the problem arises when there are too many LDLs in the bloodstream. Because more LDL particles mean more chances of these LDLs squeezing into the artery walls to form plaques. Over time, the growing plaque will narrow the arteries and even cause them to rupture, eventually resulting in cardiovascular diseases (CDs) or stroke.

So, the message is clear: the key to reducing the risk of developing CDs or stroke is to reduce the number of LDL cholesterols in the bloodstream.

And the basic and arguably the most important intervention will be to maintain a healthy diet, among other lifestyles. Because ultimately, TG and cholesterol are supplied through the diet, even the components stored in the adipocytes that are used for de novo synthesis.

Nevertheless, for some individuals, controlling their LDL cholesterol levels will require more than just a healthy diet, lifestyle, and discipline. In this case, statins may be necessary.

“To make progress in the battle against heart disease and stroke, we must encourage exercise, improve our diets still further, stop smoking, and where appropriate offer statins to people at risk.”

Statins

Statins are drugs that stop the production of cholesterols through de novo synthesis. They inhibit an enzyme called HMG-CoA reductase, which helps convert a biomolecule — HMG-CoA — to mevalonate — a precursor of cholesterols.

Examples of statins are Atorvastatin, Fluvastatin, Lovastatin, Pitavastatin, Pravastatin, Rosuvastatin calcium, and Simvastatin.

According to the National Institute for Health and Care Excellence (NICE) of the U.K., the American College of Cardiology/American Heart Association Task Force (ACA/AHA), and the European Society of Cardiology and European Atherosclerosis Society (ESC/EAS), statins should be prescribed as a preventive measure to patients with a high risk of developing CDs.

By high risk, it means people with conditions like having,

• ≥10% (or for Europeans ≥5%) risk of developing cardiovascular diseases within the next 10 years, which can be assessed on your own using the QRISK calculator, or SCORE (for Europeans).
• type 1 or type 2 diabetes.
• a family or own history of myocardial infarction (heart attack), acute coronary syndrome (any conditions that result in a reduced blood flow to the heart), coronary revascularization (e.g., stent placement or coronary artery bypass grafting), or stroke.
• moderate to severe chronic kidney disease (eGFR <60 mL/min/1.73 m²).
• metabolic genetic disorders like familial dyslipidemia or familial hypercholesterolemia (a constantly high amount of LDL cholesterols in the bloodstream due to impaired ability to clear off circulating LDL cholesterols).
• markedly elevated risk factors: Total cholesterol (>8 mmol/L or >310 mg/dL), LDL cholesterol (>4.9 mmol/L or >190 mg/dL), or blood pressure (≥180/110 mmHg).

As for individuals at low or moderate risk of heart diseases (i.e., <10% risk of developing CVD within the next 10 years), the NICE recommends prioritizing lifestyle changes before considering statins as a preventive measure.

Since extensive reviews have shown that treating 10 000 patients for 5 years with a standard statin regimen (e.g., atorvastatin 40 mg daily) would be expected to cause,

• ~5 cases of myopathy
• 50–100 new cases of diabetes
• 5–10 cases of hemorrhagic strokes.

Other side effects that were less documented include muscle pain, memory loss and confusion, unusual fatigue, digestive problems, and liver problems.

And to people that belong to this category (low or moderate risk), the benefits of statins may not justify the risks, considering that only 1 out of 140 low-risk individuals will benefit from a five-year statin prophylactic therapy.

As Professor Mark Baker, Director of the Centre for Clinical Practice at NICE said, “to make progress in the battle against heart disease and stroke, we must encourage exercise, improve our diets still further, stop smoking, and where appropriate offer statins to people at risk.”

Regardless, do note that it is important to always consult your doctor before deciding to take or ditch the statins. This article serves only to provide basic information to help you understand so that if necessary, you can engage in a better discussion with your doctor to come up with the best treatment for you.

Update: As DS Racer has pointed out, grapefruit juice may interact with some types of statins, potentially increasing the risk of side effects related to the medications. I have detailed the grapefruit juice-statins interaction and whether you should be concerned about it in the following article:

Here’s another article on HDL cholesterol:

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