Is high cholesterol just due to “eating too well”?

Case Background

Mr. Wang is 43 years old this year. He is in great health and enjoys eating. This year, the company provided these healthy employees with free genetic tests designed specifically for healthy people, which are related to the risk of hereditary cardiovascular disease and personalized medication. Not only can they detect the risk of hereditary cardiovascular disease, but they can also get their own "Individualized Medication Instructions for Cardiovascular Disease". When Mr. Wang heard this, he thought it was free and he could learn so much, so he decided to do it! Mr. Wang signed the relevant informed consent form and confidently told the staff of the testing company that he was in very good health!!!

The test results surprised Mr. Wang!

I thought the test results should be normal, but reality dealt a fatal blow to Mr. Wang. The genetic test report showed that Mr. Wang carried a heterozygous pathogenic variant on the APOB gene, which was clearly associated with a hereditary dyslipidemia, familial hypercholesterolemia (FH). The staff of the testing company contacted Mr. Wang as soon as possible and asked about the results of his most recent physical examination. It turned out that Mr. Wang's total cholesterol and bad cholesterol, low-density lipoprotein cholesterol (LDL-C), had increased significantly, 6.64 mmol/L (normal range 2.8-5.7 mmol/L) and 4.72 mmol/L (normal range <4.0 mmol/L), respectively, and had lasted for some time. Before, Mr. Wang always thought that his high blood lipids were caused by his recent busy work and social activities, and eating too much meat and fish. As long as this period of time passed, he would be able to return to normal by eating a lighter diet and exercising, so there was no need to take medicine or go to the hospital.

However, according to the consensus of Chinese experts on FH, a positive genetic test result that finds a clear pathogenic mutation is the gold standard for diagnosing FH. Therefore, Mr. Wang can be directly diagnosed with FH. His elevated total cholesterol and LDL-C are also due to the APOB pathogenic mutation he carries, not simply due to poor living habits as he thought. Compared with those people who have high blood lipids due to acquired metabolic disorders, FH patients cannot lower their cholesterol levels to a safe range simply by adjusting their diet and exercising. Through further inquiries, the staff also learned that Mr. Wang’s mother has also been taking statins to control LDL-C levels. Then Mr. Wang’s pathogenic mutation is likely to be inherited from his mother who also has high cholesterol, and there is a 50% chance that it will be passed on to his offspring. After knowing that his diagnosed FH would be passed on to the next generation, Mr. Wang suddenly became nervous and didn’t know what he should do?

What kind of disease is FH?

FH is an autosomal (co)dominant genetic disease, with genetic factors accounting for 60%-80%. Its main clinical manifestation is a significantly increased serum LDL-C level. Some patients may develop xanthomas on the skin/tendons, and may even develop coronary heart disease in their prime.

FH can be divided into two categories: homozygous familial hypercholesterolemia (HoFH) (≥2 mutations), which has more severe clinical manifestations, and heterozygous familial hypercholesterolemia (HeFH) (1 mutation), which has milder manifestations and is often missed. HeFH is actually quite common in clinical practice, with about 1 in every 200-250 people suffering from the disease, but most of the clinical manifestations are only elevated serum LDL-C levels. However, like Mr. Wang, people often do not delve into the actual cause behind the elevated LDL-C levels. Even if coronary heart disease occurs, most of them use symptomatic treatments such as stent placement, which is also the main reason for the low diagnosis and treatment rates of FH worldwide.

Xanthomas and corneal arcus that may occur in patients with FH

What should Mr. Wang do? (The significance of genetic testing)

According to the consensus of Chinese experts on FH screening and diagnosis, after Mr. Wang was diagnosed with FH through genetic testing, he should immediately start cholesterol-lowering drug treatment to control LDL-C levels within the normal range, so as to reduce the risk of coronary heart disease and improve prognosis. Domestic and foreign expert consensus and guidelines also recommend that the mutation site should be screened for the immediate family members of individuals with clear pathogenic mutations. It has been verified that Mr. Wang's 13-year-old asymptomatic daughter also carries this pathogenic mutation and is at risk of FH in the future. According to the guideline recommendations (Figure 1), preventive lipid-lowering treatment can be taken, which can significantly delay the age of coronary heart disease and truly prepare for a rainy day!

Of course, if Mr. Wang and his daughter want a healthy baby in the future, they can also prevent future babies from getting sick through selective fertility (such as prenatal screening or preimplantation genetic screening).

Figure 1. Early diagnosis and early treatment are of great significance to the prognosis of patients with familial hypercholesterolemia (FH), and can significantly delay the age of coronary heart disease. Generally speaking, the low-density lipoprotein (LDL-C) of individuals without FH accumulates to the level of coronary heart disease at around 55 years old, while heterozygous FH patients may develop coronary heart disease at around 35 years old, and homozygous FH patients may even develop coronary heart disease as early as 12.5 years old. At the same time, smoking, diabetes, hypertension, elevated triglycerides and lipoprotein (a), and decreased high-density lipoprotein (HDL-C) are risk factors for coronary heart disease, and the age of onset in women is later than that in men with the same conditions.

Case summary

In daily life, high blood lipids seem to have become synonymous with "eating too well", and there are countless people who share the same idea as Mr. Wang. After discovering high blood lipids, people often think of lowering blood lipids through exercise and diet control rather than taking medicine. However, little do people know that some types of "high blood lipids" are innate, and lifestyle improvements alone cannot completely restore them to normal. They must be combined with drug treatment and other means to control blood lipids within a safe range.

If you have ever had "high blood lipids", especially high LDL-C, don't be too immersed in the world of "eating too well". See a doctor in time to make a clear diagnosis of whether it is a genetic dyslipidemia including FH, so as to make an accurate diagnosis, early diagnosis and early treatment, delay or even avoid the occurrence of coronary heart disease! After finding a clear genetic cause, it can also help identify relatives in the family who are also at risk of the disease, just like Mr. Wang's underage daughter, so as to guide eugenics and avoid further transmission of the disease in the family.

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