Is it harmful to lower the "bad cholesterol" too low?

Many people who have existing cardiovascular disease problems or are at high risk for cardiovascular disease know the importance of lipid control. Dyslipidemia, especially elevated total cholesterol and LDL cholesterol, are the underlying risk factors for atherosclerosis, and plaque formation, and it is particularly important to actively control lipid levels, especially the "bad cholesterol" LDL cholesterol, in the prevention of cardiovascular disease.

In the new dyslipidemia guidelines published in 2019 by the European Society of Cardiology and European Atherosclerosis, one of the more subversive messages given in the guidelines is that there is no lower limit to the control of LDL cholesterol for the prevention of cardiovascular disease, that is, the guidelines conclude, based on a combination of relevant clinical evidence, that the lower the LDL cholesterol, the lower the risk of cardiovascular disease The lower the LDL cholesterol, the lower the risk of cardiovascular disease.

With such foreign guideline recommendations, many of you are convinced that this is correct, but is it true that the lower the LDL cholesterol, the better? In today's article, we will discuss with you some ideas and contents that are different from the guideline recommendations.

"Bad cholesterol" is only relative

Many of you think that cholesterol is a "bad thing", but, without cholesterol, life would not exist at all. Lipid nutrition is one of the three essential nutrients for the human body, and cholesterol is essential for the formation of cell membranes for cell division and the synthesis of hormones. When LDL cholesterol is within the normal range, it plays an important role in maintaining normal cell division and reproduction in our body, synthesizing hormones, and forming bile acids.

When there are risk factors for cardiovascular disease or people with existing cardiovascular disease and LDL cholesterol levels are outside the normal range, this excess "cholesterol" will gradually deposit under the endothelium of the blood vessel wall, accelerating the progression of atherosclerosis and increasing the risk of cardiovascular disease, and in this case, active control of LDL cholesterol levels is an important control target to reduce the risk of cardiovascular disease.

What is the safe level of lipid control?

For healthy people at low risk of cardiovascular disease, a normal LDL cholesterol level in the blood is below 3.4 mmol/L. For people at high risk of cardiovascular disease, controlling LDL cholesterol in the blood to below 2.6 mmol/L can help reduce the chance of cardiovascular disease; and for people with existing cardiovascular disease problems, such as those who have had a heart attack, it can help reduce the chance of cardiovascular disease. For people with existing cardiovascular problems, such as those who have had major cardiovascular events such as heart attacks and brain attacks, LDL cholesterol should be controlled to less than 1.8 mmol/L.

If you can control LDL cholesterol below 1.8 mmol/L, do you still need to go lower? Is it really the lower the better? In fact, those who make this argument miss an important point, which is that cholesterol is not a useless waste product, but an essential nutrient that the body needs. Looking at the data from certain large clinical studies, it does seem that keeping cholesterol at an extremely low level can further reduce the risk of problems such as heart attacks and brain attacks, but this extremely low level of LDL cholesterol may, in another way, lead to nutritional imbalances in the body, which in turn can lead to other health risks.

Blood lipids will be too low and may pose two major health risks

There are studies on how much LDL cholesterol can be lowered without risk, and similarly, there are studies on the health risks associated with dropping LDL cholesterol too low. Here we will briefly share 2 relevant studies conducted around Chinese people to share with you the possible risks associated with lowered blood lipids.

In 2020, a study from Ruijin Hospital of Shanghai Jiao Tong University, which included 137,800 subjects in the Chinese Cardiometabolic Disease and Cancer Cohort Study, examined the relationship between lipid and blood glucose levels and the risk of cancer in subjects with LDL cholesterol above 3.4 mmol/L compared to those with LDL cholesterol less than 1 mmol/L. The results of the study showed a 48% increased cancer risk in people with LDL cholesterol less than 1.8 mmol/L, and the greatest increase in cancer risk especially in people with diabetic problems, poor glycemic control, and low control of lipid levels.

In a study published in Nature Medicine in 2019, a collaboration between Peking University and the China Food and Drug Safety Risk Assessment Center, a sample of more than 500,000 Chinese people analyzed the causal relationship between lipid control levels and brain infarction and brain hemorrhage in Chinese adults and showed through nearly 10 years of follow-up data that no reduction in LDL cholesterol of The data showed that a 1 mmol/L reduction in LDL cholesterol was associated with a 20% reduction in the risk of cerebral infarction but a 17% increase in the risk of hemorrhagic stroke.

As with large clinical studies that suggest that lower LDL cholesterol is better, such studies may be flawed in one way or another and should not be used as a reference for everyone, but they do suggest that lower LDL cholesterol is not better, and the resulting health risks are a cause for concern.

2 groups of people who should avoid lowering their lipids too low

When it comes to controlling the risk of cardiovascular disease, there is no disputing the fact that blood lipids should be strictly controlled. However, we should make individualized analyses and judgments on how to control lipids and how much control is enough, taking into account the actual situation. The data and probabilities given in the guidelines and large clinical studies are based on a statistical analysis of big data, and each individual person's situation may be very different, so it may not be the best choice to set an overly strict lipid control goal for yourself without evaluating your actual situation because you believe in a certain study or guideline. The best choice may not be the best one.

Combining the 2 studies mentioned above, here we suggest that those who have the following two types of conditions should not lower their blood lipids too low.

The first is those who have diabetes and poor glycemic control, along with high-risk factors for GI cancer. For example, if you have a family history of cancer or have pre-cancerous lesions, you should pay more attention to controlling your blood lipid level and avoid lowering LDL cholesterol too low. On the one hand, these patients should actively control their blood glucose level and keep their glycosylated hemoglobin level below 7.0% to ensure safety, and on the other hand, they should pay attention to the reasonable control of LDL cholesterol. For example, in patients with existing cardiovascular disease, it is sufficient to control LDL cholesterol to about 1.8 mmol/L, and it is not necessary to lower it too low at all.

The second group is those who have a high risk of a brain hemorrhage. Both cerebral infarction and cerebral hemorrhage are closely related to the progression of atherosclerosis, but there is a certain contradiction in controlling the risk. By further reducing the lipid level based on controlling LDL cholesterol to 1.8 mmol/L, the risk of cerebral infarction can still be reduced, but the risk of cerebral hemorrhage will be further increased. If there are people at high risk of cerebral hemorrhage with poorly controlled hypertension or cerebral arterial vascular amyloidosis, it is also still recommended to set a control target of about 1.8 mmol/L, and there is no need to lower it too low.

In conclusion, when setting lipid control goals, we should not only consider the requirements of the guidelines but also make rational and personalized assessments and judgments, taking into account our actual conditions. If we can actively control other chronic disease factors and people with a low risk of cancer and cerebral hemorrhage but a high risk of heart attack and cerebral infarction, we can certainly consider lowering LDL cholesterol control; however, for people who are not at high risk of thrombosis but have a certain risk of cerebral hemorrhage and cancer, lowering lipid level too low may bring certain risks and outweigh the losses.