The cause of cardiovascular disease is not only "bad" cholesterol: what genetics says about it

Cardiovascular diseases are approximately 40–50% related to hereditary factors(Craig et al., 2022). Therefore, the assessment of cardiovascular risks is not limited to the cholesterol level in a blood test.

Heart and vascular health is influenced by genetic factors related to inflammation, susceptibility to high blood pressure, the body's response to salt and stress, and blood clotting mechanisms. Most of these factors are not reflected in standard laboratory tests, so a person may not know about them for years until the first clinical manifestations will not appear.

What is usually measured to assess health?heart and blood vessels, and what remains aside

Cholesterol is important. The link between elevated LDL levels and the development of atherosclerosis is well documented in cardiology. But cholesterol– only one of the players in a much more complicated game.

The cardiovascular system responds to dozens of factors simultaneously: how the body regulates blood pressure, how it deals with inflammation in the vascular wall, how efficiently it removes certain metabolites, how the heart muscle responds to stress. None of the standard tests cover this picture holistically.

Even with normal levels of "good" cholesterol, there may be elevated homocysteine, chronic latent inflammation, or a hereditary predisposition to hypertension, which is only partially corrected by lifestyle.All this goes unnoticed until the first symptom appears.

What other factors affect the health of the heart and blood vessels?

Approaches to the prevention and treatment of cardiac diseases have long gone beyond the correction of cholesterol and blood pressure.

What else shapes real cardiovascular risk, particularly at the DNA level, but rarely makes it onto the standard screening list?

• Homocysteine –an amino acid, elevated levels of which damage the inner surface of blood vessels and are associated with the risk of heart attack and stroke.A large meta-analysis of Mendelian randomization (Yuan et al.,BMC Medicine, 2021) based on data from over 44,000 people confirmed: genetically determined elevated homocysteine ​​levels are associated with an increased risk of stroke – each standard deviation has an OR ≈ 1.11 (95% CI 1.03–1.21).

• C-reactive protein (CRP)– a marker of systemic inflammation. Both indicators depend on both nutrition and hereditary metabolic characteristics. The largest GWAS on CRP (Said et al.,Nature Communications, 2022), which included more than 575,000 people, identified 266 independent genetic loci that affect the level of systemic inflammation, 211 of which are described for the first time. This confirms:The predisposition to chronic vascular inflammation is largely hereditary.

• Full lipid profile: aboutIn addition to total cholesterol, its fractions are fundamentally important: HDL ("good" cholesterol), apolipoprotein A1, triglycerides. A person can have acceptable total cholesterol–and at the same time an unfavorable balance of lipid fractions, which forms imperceptibly over the years.

• Reaction to salt and pressure: butSome people react to increased sodium intake with a marked increase in blood pressure. In others,–almost nothing. This difference is due not only to the amount of salt in the diet, but also to how they react to blood vessels and kidneys–and this is to a large extent hereditary feature.

• Prone to rhythm disturbances: atrial fibrillation (atrial fibrillation) can not show noticeable symptoms for years–and at the same time significantly increase the risk of stroke. Tendency to this pathology is partly hereditary. GWASmeta analysis (Choi et al.,Nature Genetics, 2025), covering over 180,000 cases, identified over 350 genetic loci associated with atrial fibrillation.PRS, built on these data, significantly improved risk prediction compared to standard clinical scales.

• Metabolic background.ne-alcoholic fatty liver disease, reduced insulin sensitivity, predisposition to gout–All of this puts a strain on the cardiovascular system even when there is no official diagnosis yet.

None of these factors are independent. They interact and reinforce each other. Therefore, the results of one analysis do not demonstrate the state of health of the heart and blood vessels as a whole.

Why people with normal cholesterol also have problems with heart

Homocysteine ​​levels and susceptibility to chronic vascular inflammation have a genetic component, related to how the body absorbs B vitamins, how it processes certain amino acids, how it responds to oxidative stress. A routine blood test will show current levels of indicators, but will not explain the reason, and will not allow you to understand whether they need to be monitored especially carefully.

The same applies to salt sensitivity. A person eats as they are used to for years, the pressure is formally kept within acceptable limits, but gradually the vessels experience a load that is not noticeable from the outside.

Hence the paradox: two people of the same age, a similar lifestyle, similar test results - and at the same time very different cardiovascular profiles after 10–15 years. This difference is partly explained by genetics.

Genetics and the heart: where is the connection

The question “If my father had a heart attack, will I have one too?” is one of the most common. The answer is that genetics shows the probability, but does not determine the outcome. A person with a strong family history can avoid cardiovascular disease if they are aware of their genetic characteristics and act according to their genetic profile.

This may be new information for many, but genetics are associated with:

• Tendency to high blood pressure and response to salt in the diet

• Features of lipid metabolism: HDL level, apolipoprotein A1, tendency to hyperlipidemia

• Level of homocysteine ​​and markers of vascular inflammation

• Tendency to heart rhythm disorders

• Metabolic risks: tendency to non-alcoholic fatty liver disease (NAFLD), impaired insulin sensitivity

At the same time, lifestyle - regular physical activity, balanced nutrition, quitting smoking and alcohol - remains a powerful factor that significantly influences how these tendencies are realized.

Heredity sets the initial conditions. The extent to which they manifest itself, depends ondailydecisions.

What you should know about your heart already today

Most cardiovascular states –They are not sudden. They are the result of processes that take years: a slow increase in blood pressure, the accumulation of inflammation, a change in lipid balance. The problem is that these processes take a long time to remain silent – ​​and not signal about either explicit symptom well.

Knowing your genetic profile of cardiovascular risks is a new dimension of understanding your own health. This allows you to see what conditions your body is prone to, what you should pay attention to now, and what lifestyle changes make the most sense for you. The purpose of genetic testing is not to find a problem, but to gain an understanding of the peculiarities of the functioning of your body and the basis for effective solutions.

Learn about the genetic features of the cardiovascular system → Genetic test for cardiovascular risks 

The heart is more than the results of tests or an electrocardiogram (ECG)

Cholesterol is an important indicator. But it is not exhaustive. Sometimes inflammatory markers, lipid fractions, salt response, susceptibility to arrhythmias and metabolic conditions are left out, which gradually affect the health of the heart and blood vessels. Some of these factors are related to genetics. It cannot be seen with traditional examinations. Knowing your genetic profile means being able to act proactively - to prevent, not to treat.

Genetic test results–It is not a diagnosis and does not replace a doctor's consultation. The Apixmed Prism report provides genetic context that complements the results of the examinations and helps you make decisions together with your doctor.

 List of sources:

1. Craig, A., Delles, C., & Murray, E. C. (2022). A Review of Vascular Traits and Assessment Techniques, and Their Heritability. Artery Research, 28(2), 61–78. https://doi.org/10.1007/s44200-022-00016-y 

2. ‌Yuan S, Mason AM, Carter P, et al. Homocysteine, B vitamins, and cardiovascular disease: a Mendelian randomization study. BMC Med. 2021;19(1):97. https://doi.org/10.1186/s12916-021-01977-8Said S, Pazoki R, Karhunen V, et al. Genetic analysis of over half a million people characterises C-reactive protein loci. Nat Commun. 2022;13(1):2198. https://doi.org/10.1038/s41467-022-29650-5

3. Choi SH, Weng L-C, Roselli C, et al. Meta-analysis of genome-wide associations and polygenic risk prediction for atrial fibrillation in more than 180,000 cases. Nat Genet. 2025. https://doi.org/10.1038/s41588-024-02072-3