Cholesterol: it's not that simple

Cardiologist Yaroslav Ashikhmin about the "abolition" of the harm of cholesterol and the benefits of statins

Anna Kerman, XX2 century

The news about the benefits of "harmful" cholesterol and the senselessness of prescribing statins became an occasion for lively discussions in social networks: the authors of the "review of reviews" were accused of bias, and many of their conclusions seemed to our readers groundless.

Considering that the authors of the article in question are really known for their "anti-cholesterol" position, we asked the cardiologist, PhD, researcher of the Research Department of Cardiology of the I. M. Sechenov First Moscow State Medical University Yaroslav Ashikhmin to comment on this work.

– It is necessary to very clearly separate statins in primary prevention and in secondary prevention. Secondary prevention is a situation where a person has already had a stroke or heart attack, or at least has a confirmed coronary heart disease. There is no doubt that statins are the most effective means of preventing repeated heart attacks and strokes here. If a person has already had a heart attack or stroke, no cholesterol needs to be measured to make a decision about prescribing statins. Such patients should receive them automatically.

As for primary prevention, regarding the issue of prescribing statins to people who have not had heart attacks or strokes, there was no surprise for me personally in the results of this review. The position of statins in primary prevention has never been strong. And this is easily explained: for a statin to work, a person must have a formed atherosclerotic plaque (or there must be a very high risk that it will grow very quickly). Statins do not work by "lowering cholesterol", but by strengthening the fibrous covering of the atherosclerotic plaque. After the use of statins, it becomes less prone to rupture and more dense.

How did we make the decision to prescribe statins in primary prevention before? If we do not talk about specific cases, for example, if a person has a familial heterozygous form of hypercholesterolemia, then earlier we assessed the patient's risks using special calculators. The risk of heart attack and stroke, that is, diseases based on the risk of rupture of atherosclerotic plaque. The models on the basis of which these calculators work take into account gender, age, attitude to smoking, blood pressure and cholesterol levels. If the risk – according to the analysis of these factors – was assessed as high, then statins were prescribed to the person. In this case, we had a wide population of very different patients who could grow plaques. But they might not have grown.

It can be assumed that the higher the risk of plaque formation, and then the risk of plaque rupture, the higher the effectiveness of the statin. But in the modern world, many people are committed to a healthy lifestyle, and many receive medications to lower blood pressure. Therefore, it may turn out that the model does not work very well, because in this population of people plaques do not develop very often for some reason. And there will simply be no point of application of statins.

Now – literally in the period from 2016 to 2018 – there has been a paradigm shift in prevention. We try to prescribe statins in primary prevention not to those patients whose calculators show high risks, but to those who received the greatest benefit from statins in clinical trials. And as it turned out, there are not so many such patients. These are mainly patients with diabetes mellitus and patients with high levels of C-reactive protein (JUPITER study). At the same time, interestingly, they may have fairly low levels of low-density lipoproteins and cholesterol. Systemic inflammation in this case can play a significantly greater role in the formation of atherosclerotic plaques and create a substrate, a "field of action" for statins.

But we go further, and my scientific work is devoted to the preventive concept 3.0. Even if we take and prescribe statins to those populations of patients who definitely benefited from the appointment of statins, on the one hand, we can still prescribe statins unreasonably. The fact is that in this situation we still use a population–based, not an individualized approach - and a particular patient may not have a substrate. On the other hand, risk models do not include important factors associated with the rapid growth of plaques, for example, an early family history of a heart attack, a high level of social stress, the presence of rheumatological diseases, and so on. That is, this approach is also imperfect.

But within the framework of the 3.0 concept, it is possible to make the appointment of statins really individualized – for this it is necessary to see if a person has developed plaques against the background of all those risk factors that he had. It's one thing to consider virtual risks, and another to conduct a low–dose computed tomography of the heart and assess the presence of plaques. With such a study (an assessment of the calcium index is implied), the radiation load is comparable to mammography, but it allows you to find out if there are atherosclerotic plaques.

The MESA study gave us grounds to use computed tomography in the course of making a decision on prescribing statins to patients from medium and low risk groups. If there are additional factors that are not taken into account in the risk model, the appointment of statins may be appropriate.

Thus, statins are one of the tools for reducing cardiovascular mortality. But this tool only works by strengthening the tire of the atherosclerotic plaque. If we know for sure that there is a plaque, statins should be prescribed, especially if the plaque has already ruptured. If there is no plaque, then it should be understood that the appointment of statins – and they are used all their lives – is an exceptionally serious decision, which requires deep reflection. I have no reason to believe that statins will be effective in broad populations of patients without heart disease. Such patients may have a higher chance of dying from injury or cancer than from a heart attack or stroke. Or from heart failure unrelated to atherosclerosis: for example, due to ventricular tachycardia (athletes), alcoholic heart disease (our compatriots), heart failure associated with hypertension. In these diseases, there is also no point for the application of statins.

Another problem is that reading such articles, people often decide that statins are not useful to them personally. But we have a catastrophe in our country with the fact that statins are not prescribed to those patients who have already suffered a heart attack or stroke. Cholesterol targets are not reached (in those who have had a stroke or heart attack, you need to go to the most aggressive therapy to reach the recommended LDL levels, less than 1.5-1.8 mmol/l). These figures show that the statin dose is sufficient to stabilize the plaque, lowering cholesterol in itself is not an end in itself, that is, cholesterol levels are just a marker. If some "plaque strength indicator" appears, there will be no need to measure cholesterol in this context. But it is very important that people do not cancel statins, because in our country these drugs are more often not prescribed when necessary, and not vice versa.

You can expand by saying that the body is so complicated that there is a huge skepticism about medical effects in order to prolong life (I'm talking, of course, about cases when there are no diseases). Aspirin "failed" as a means of primary prevention, many other drugs failed. There is no reason to believe that the so-called mythical "geroprotectors" will also show effectiveness. I suggest people come to terms with the fact that now we do not have – and most likely will not have in the near future – medication measures to effectively prevent death in people who feel healthy and without an obvious significant genetic substrate that ensures early death (such as prolongation of the QT interval or familial heterozygous form of hypercholesterolemia). But drugs can, of course, significantly improve the quality of life.

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