Alpha and Omega-3: algorithm developed in Russia to improve atherosclerosis therapy

Russian scientists have developed a new approach to the diagnosis and monitoring of atherosclerosis based on the profiling of fatty acids in blood plasma. A decrease in the level of these substances may indicate inflammation in the walls of blood vessels and the presence of dangerous plaques prone to rupture, which leads to heart attacks and strokes. How the level of omega-3 in blood plasma and cardiovascular diseases are related and how the development will help — in the Izvestia material.

An algorithm for monitoring atherosclerosis

Scientists at Sechenov University have created a model for detecting "dangerous" atherosclerotic plaques using a blood test. According to them, atherosclerosis is one of the key diseases of the cardiovascular system underlying heart attacks and strokes. The basis of modern therapy is the appointment of statins, however, a more in-depth biochemical diagnosis is required to fully assess the risks and effectiveness of treatment.

In the new study, scientists focused on the so-called omega—3 index, an indicator that reflects the level of omega-3 polyunsaturated fatty acids (EPA and DHA) in the membranes of red blood cells. This index is considered an important prognostic marker of cardiovascular diseases: its value below 4% is associated with an increased risk of disease progression.

The problem is that the standard definition of the omega-3 index requires an analysis of red blood cells, which is not always available in routine practice. Scientists have proposed a solution: They have developed a mathematical model that makes it possible to accurately estimate the omega-3 index based on blood plasma analysis, a simpler and more common test.

The model was built on the basis of data from 69 volunteers from Moscow and adapted to the nutritional and metabolic characteristics of the Russian population. This makes the development especially relevant for use in domestic clinical practice.

During the study, the researchers analyzed blood samples from 52 patients with confirmed atherosclerosis and 50 healthy volunteers. In patients with atherosclerosis, researchers have identified significant changes in the profile of fatty acids, including a decrease in the proportion of omega-3 and impaired activity of enzymes involved in their metabolism. Statin therapy has also been shown to partially normalize the lipid profile, but it does not always lead to a sufficient increase in omega-3 levels.

—We have built our own model of the relationship between the level of omega-3 from plasma and in red blood cells with the instability of atherosclerotic plaques for the Russian population," Philip Kopylov, director of the Institute of Personalized Cardiology, explained to Izvestia. — The analysis showed that unstable levels of DHA and other omega-3 fatty acids are significantly lower than in stable ones. This suggests a potential role for omega-3 fatty acids in maintaining plaque strength. Our model allows us to estimate this indicator by plasma, which simplifies monitoring of patients' condition.

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The developed algorithm allows not only to assess the patient's current condition, but also to predict the effectiveness of therapy, as well as to justify the need for additional omega-3 drugs. This opens the way to a personalized approach in cardiology practice.

The new method can be integrated into a laboratory diagnostic system in the coming years. The scientists plan to continue their research to confirm the clinical significance of the development in large cohorts of patients.

What does a reduced level of fatty acids mean?

A low omega-3 index is associated with an increased risk and instability of plaques. But it needs to be interpreted in combination with other indicators — C-reactive protein, smoking factor, and so on, Albert Rizvanov, head of the Personalized Medicine Center of Excellence at Kazan (Volga Region) Federal University, told Izvestia. The decision to take omega-3 must be made by a doctor. Although these polyunsaturated fatty acids are widely used as dietary supplements today, they need to be used consciously.

Omega-3 fatty acids reduce inflammation in the vascular wall, affect the "fluidity" of membranes and blood clotting processes. When they are deficient, plaques become more "brittle" and prone to rupture, which leads to heart attacks and strokes, the scientist said.

The new algorithm will help to screen people with high cardiovascular risk and select patients for in-depth examination (ultrasound, CT). Another important use is that such software helps to understand when it is worth adding omega—3 drugs to statins and whether there is an effect from this. This is not a replacement for standard therapy, but an "add-on" to make it more accurate, Albert Rizvanov noted. At the same time, the plasma test is simpler and cheaper. But, like any algorithm, the model needs to be tested on large and diverse groups of patients, taking into account diet, season, concomitant therapy, and laboratory features.

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The results of the published study do not pretend to be a cardinal solution to the issue, since they are devoted only to one of the factors — lipid metabolism disorders (dyslipidemia), and its rather narrow component is omega—3, said Professor Lyudmila Salamatina, cardiologist at the Center Plus medical clinic of the Central Research Institute of Epidemiology of Rospotrebnadzor.

— Scientists have tried to uncover the causes of atherosclerosis at the molecular level, which requires special equipment and skills. The authors analyzed the initial profile of fatty acids in blood plasma and plaques in patients receiving standard treatment without changing existing therapy regimens or taking omega-3 supplements. The data obtained are preliminary and require further confirmation, greater reliability (an increase in the number of people examined), and consideration of other related factors. Therefore, in the near future we will not see their use in clinical practice, and even more so for mass population prevention," the specialist said.

The time from the beginning of research to practical application is sometimes calculated in years. For example, about 50 years have passed from the discovery to the widespread clinical use of statins in cardiology, the professor emphasized. However, research needs to be continued.

The results of the work, supported by a grant from the Russian Science Foundation, are published in the journal Biomedicines.