Affairs of the heart
How to deal with the main disease of the XXI century
A third of deaths in the world and almost half in Russia accounts for cardiovascular diseases. Evolution has not prepared man for the abundance of modern life: our vessels are well protected from external damage, but not from fatty foods, smoking, alcohol and chronic stress. Cardiologist Yaroslav Ashikhmin told post-SCIENCE about how cardiovascular diseases arise, what they are and why they are dangerous.
On January 30, a rare event happened at a football match in France: right during the game, the coach of one of the teams ran out onto the field and rushed headlong to his player, overtaking even the club doctors. His goalkeeper, a healthy 20-year-old guy, collapsed for no reason as if knocked down in a swoon. Later, doctors will say that this is an attack of tachycardia, which can lead to deterioration of the heart and provoke the development of heart failure. A dangerous disease that almost ended the career of a young French athlete belongs to a wide class of cardiovascular diseases - one of the main problems of our time.
According to WHO, cardiovascular diseases (CVD) – this is the main cause of death worldwide, in 2019, 27% of all deaths were due to CVD. For example, arterial hypertension is considered one of the most common diseases in the world: it is detected in 30-40% of all adults. In Russia, slightly less than half of deaths are associated with heart attack, hypertension and stroke (according to Rosstat).The development of cardiovascular diseases can be divided into three key blocks: atherosclerosis, that is, the accumulation of fatty (lipid) plaques in the vessels, arterial hypertension and sudden cardiac death. One way or another, atherosclerosis and hypertension can lead to heart attack, stroke and dementia (colloquially – dementia), and the final path of development of all heart diseases is chronic heart failure. In our article, we will consider the causes of CVD, the mechanisms of their development and what methods of prevention will help in the fight against them.
Causes of CVD: male gender, chronic stress and poor nutrition
Over the past millennia, the risk factors for cardiovascular diseases have changed a lot. Surprisingly, lifestyle, including food, is to blame for everything. Previously, people lived in conditions of chronic lack of food, death more often occurred due to damage to blood vessels from the outside. Therefore, our vessels are well protected from such damage. However, in conditions of modern abundance, when atherosclerotic plaques are formed due to improper nutrition (they consist of "bad fats", including cholesterol, and various cells, including macrophages, unable to digest it), they appear on the inside of the vessel. Nature was not ready for this.
Currently, the development of cardiovascular diseases is influenced by two groups of risk factors: internal, that is, genetic, and external. For example, the development of atherosclerosis and hypertension: male gender, age, smoking, obesity, diabetes mellitus, lipid metabolism disorders, chronic stress, depression and other factors.
Why is it the male sex in the risk group? Women are most often characterized by natural care for offspring and, as a result, a careful attitude towards themselves, and their behavior is more protective.
There are also a number of genetic factors. Today, their contribution is being actively studied, but genetic risk assessment systems are far from perfect. For example, if we are talking about arterial hypertension, latent heredity makes a big contribution. That is, scientists know that patients whose relatives suffer from hypertension have a sharply increased risk of its development. At the same time, science has not yet been able to clearly identify half of the genes and gene interactions that contribute to the development of the disease.
Risk assessment: what has the accumulated data changed?
Now, to assess the risk of developing cardiovascular diseases, the SCORE calculator (Systematic COronary Risk Evaluation) is most often used, which helps to calculate the risk of fatal cardiovascular diseases over the next 10 years. It compares gender, age, smoking attitudes, systolic blood pressure and cholesterol levels and calculates the total cardiovascular risk: from 1 to 5% - moderate risk, 5-10% – high, over 10% – very high.
At the same time, not always available risk factors, such as smoking or elevated cholesterol levels, can lead to the development of the disease. Therefore, now there is a transition from simple risk models to prevention, adjusted taking into account the results of clinical trials. Now, for example, in the UK there is a huge biobank in which biomarkers, pressure levels and fully sequenced exomes and genomes are accumulated, and a model based on these data, more precisely, risks calculated using SCORE systems.
In parallel, methods of searching for morphological changes, that is, specific changes associated with the onset of the disease, are actively developing. Perhaps soon we will see a transition to the concept of prevention 3.0, which is based on radiation and molecular diagnostics of very early changes in blood vessels and the heart. For example, using the level of coronary calcium or C-reactive protein, which reflects systemic inflammation, it is possible to understand whether atherosclerosis of blood vessels develops. A more accurate assessment methodology will determine whether there are atherosclerotic plaques in the vessels.
How atherosclerosis and arterial hypertension occur
Atherosclerosis is a disease in which cholesterol plaques and fats are deposited on the walls of blood vessels in the form of plaque. First of all, this applies to the arteries of the heart, carotid and cerebral arteries. The early stages of atherosclerosis have not been studied very well yet. But we can say that immune system cells are involved in the process, smoking and air pollution play a role. And we know exactly what each of the stages of this process looks like.
Drawings by Katya Zolotareva
Immune cells begin to "crawl" under the inner lining of blood vessels, like under a blanket. Because of this, the permeability of the inner lining of blood vessels to low-density lipoproteins increases – these are particles that carry cholesterol. In addition, when the level of low-density lipoprotein cholesterol (also called bad cholesterol) exceeds 4.9 millimoles per liter, it itself begins to stimulate inflammation. To get rid of lipids from the inner lining of blood vessels, the immune system sends macrophages whose task is to absorb a variety of cellular debris. But since macrophages do not have a system for splitting lipids, they die and fill the nucleus of the atherosclerotic plaque. The plaque grows, and when its cap becomes unstable, the contents are released into the vessel. The vessel becomes clogged, a blood clot forms, and the tissue that is located lower in the bloodstream dies – in the heart this process is called a heart attack, in the brain – an ischemic stroke.
Arterial hypertension, which is periodically confused with atherosclerosis, is a persistent increase in blood pressure; it primarily concerns the middle lining of the vessels (media). Due to the increase in pressure, the likelihood of stroke, heart attack, dementia and kidney failure increases. The risk of cardiovascular diseases appears at a pressure of 120/75, the limit of arterial hypertension is 140/90 (at home 135/85). An increase in systolic pressure by 20, and diastolic pressure by 10 millimeters of mercury increases the risk of coronary heart disease twice.
Blood pressure is determined by three key factors: heart rate, the volume of circulating fluid, which is regulated by the kidneys, and vascular resistance, which is determined by the degree of tone of peripheral vessels (for example, the arteries of the upper and lower extremities, visceral or carotid arteries). Three factors influence its growth. The first is a violation of the function of the immune system, which is superimposed with chronic stress. The second etiological factor is an increase in the activity of the sympathetic nervous system ("adrenaline level"). The third is fluid retention by the kidneys associated with disruption of the renin-angiotensin-aldosterone system. All this is influenced by genetic features.
While scientists do not understand its etiology very well, that is, the causes of its occurrence. If we are talking about secondary, that is, symptomatic hypertension, the factors of development may be thyroid pathology, excessive production of hormones by the adrenal glands, increased cortisol secretion, narrowing of the renal arteries, stenosis of the renal arteries. But in 90% of cases, if a person falls ill with so-called essential hypertension, it is impossible to understand and find the early cause of an increase in blood pressure.
One of the promising concepts of the occurrence of essential (that is, without a clear reason) arterial hypertension is a violation of the function of the immune system, which is superimposed with chronic stress. Immune cells in a number of situations – against the background of hereditary predisposition, increased salt intake and chronic stress – begin to "work incorrectly". They get into certain regions of the brain, causing inflammation there, they can get into the kidney tissue and peripheral vessels. Penetrating into the kidney tissue, immune cells stimulate sodium retention, thereby retaining fluid and increasing diastolic pressure. These immune mechanisms are being actively studied, but there is no full-fledged concept yet.
But the further mechanisms are well known. Initially, the level of adrenaline and heart rate increases, blood vessels narrow, prehypertension develops, which then turns into persistent hypertension. This is followed by vascular damage, which leads to damage to the white matter of the brain and dementia. Hypertension-associated renal tissue fibrosis leads to the development of renal failure. Changes in the blood vessels of the brain, coupled with atherosclerosis, dramatically increases the risk of stroke.
But this is not all the troubles: among other things, hypertension leads to stroke, both hemorrhagic, that is, associated with hemorrhage, and ischemic, associated with thrombosis. It also causes damage to the white matter of the brain, followed by dementia. In relation to the heart, arterial hypertension increases the risk of myocardial infarction and leads to heart failure.
Yaroslav Ashikhmin: "I believe that a Nobel Prize will be awarded for the discovery of a clear cause of hypertension."
Sudden cardiac death
Sudden cardiac death is associated with life–threatening arrhythmias - the third of the key blocks of CVD development. Arrhythmia is any heart rhythm that differs from the normal sinus rhythm. Here the main role is played by ventricular tachycardia, that is, accelerated work of the ventricles of the heart. Most often, its development is due to a genetic predisposition, and tachycardia is associated with the structural features of the ion channels of heart cells – cardiomyocytes.
It is often enough to make one cardiogram to identify changes on it that will indicate an increased risk of sudden cardiac death. For example, this way you can detect Brugada is a pattern that leads to Brugada syndrome. Patients have an increased risk of ventricular tachycardia, and if there have been cases of sudden cardiac death in the family, they are definitely at high risk.
If the risk is very high, then the only method of preventing sudden cardiac death in patients will be the installation of a cardioverter-defibrillator. This is a device that constantly monitors the heart rate and, in the case of ventricular tachycardia, can give an electric pulse of sufficiently high intensity. Thus, it will return the normal sinus rhythm and prevent sudden cardiac death.
The incidence of heart failure increases with age, so older patients have a higher risk of ventricular tachycardia. But it does not spare even people who carefully monitor their health: according to various estimates, one out of 40,000 or even 80,000 athletes die from sudden cardiac death.
Another solution has shown its effectiveness in Monaco, where there are many elderly people: according to the census, 25% of the population of the principality is over 65 years old – defibrillators were installed in public places there. The terminals of an automatic defibrillator are glued to a person's chest, the device automatically identifies a pathological rhythm and causes an electric shock.
Prevention of cardiovascular diseases
There are two strategies for the treatment and prevention of cardiovascular diseases, depending on whose interests are put first. If these are the interests of the public health system, then choose a model based on the assessment of inexpensive risk factors using well-proven measures. This strategy leads to a reduction in overall mortality, a reduction in risks, but because of its promiscuity, it will definitely hook patients who do not need therapy. There are patients who have a high risk, but atherosclerosis or hypertension will never develop.
But all medications have side effects. If you look at society as a whole, the risk of side effects is lower than the risks associated with complications. However, there is a group of patients in whom the risk of side effects exceeds the risk of complications. And the concept of prevention aimed at the interests of the healthcare system will not see these people.
Therefore, there is another approach based on an individual approach, the purpose of which is to assess molecular disorders and, taking into account all risk factors, choose the appropriate therapy. The difference between the two strategies is obvious: the first is cheaper, so it will be common in poor countries, and the second involves spending a lot of resources, therefore, it will be developed and practiced by rich states.
If we are talking about primary prevention, it is often enough to take measures to change the lifestyle. The standard concept sounds like this: to intensify prevention for patients at high risk of diseases. The higher the risk, the more intensive measures should be taken to prevent cardiovascular disasters.
In the early stages, it is possible to prevent the development of cardiovascular diseases with the help of simple WHO recommendations. It is necessary to reduce the use of tobacco and alcohol, increase physical activity, eat right and fight obesity. If you have hypertension, limit salt intake: it retains fluid in the body and increases blood pressure.
With secondary prevention, it is no longer possible to do without medicines. Cholesterol-lowering medications are used for atherosclerosis: statins, PCSK-9 inhibitors, new targeted drugs. If the plaque is about to burst, antithrombotic drugs are prescribed, including aspirin, clopidogrel, ticagrelor. They, like a climber's insurance, work only at the last moment, preventing the formation of blood clots. Gradually, anti-inflammatory therapy also penetrates here. For example, the monoclonal antibody Kanakinumab can dramatically reduce the risk of cardiovascular disasters due to its anti-inflammatory actions.
In the case of hypertension, drug therapy is prescribed: ACE inhibitors, sartan class drugs, calcium channel blockers and diuretics that affect the volume of circulating blood. Previously, beta blockers were used, which reduce the heart rate. But today they are placed in the second line, because they do not prevent stroke so well. It is also known that the use of antihypertensive drugs is accompanied by normalization of blood pressure, leads to a dramatic reduction in the risk of stroke and to a serious reduction in the risk of heart attack and kidney damage.
Recently completed the study of polypilli (polypilli) – tablets that simultaneously contain drugs for the treatment of hypertension, statin and aspirin. The therapy proved to be effective for a high-risk patient, even with an unknown status regarding the presence of plaques. The polypill increases adherence to treatment, thereby reducing the development of myocardial infarction, stroke and chronic heart failure.
Coffee, alcohol and blood tests
There are several popular opinions about what exactly helps with the primary prevention of cardiovascular diseases - for example, coffee, blood tests and a little alcohol. From this list, the easiest way is with coffee: daily consumption of a drink in the amount of 3-4 cups of espresso reduces the risk of cardiovascular diseases.As for blood tests, everything is already more complicated. You need to control cholesterol levels, blood pressure levels and C-reactive protein. It is possible to do a cardiogram once to understand that you have no risk factors for sudden cardiac death. If you know about a hereditary predisposition – there were cardiovascular catastrophes in the father before the age of 55 or in the mother before the age of 65 - it is necessary to study biomarkers in the blood in detail.
And it's very difficult with alcohol. In population studies, scientists have found that 1-2 doses of alcohol taken daily by study participants can reduce the risk of coronary heart disease. But such studies are ambiguous and raise questions.
Especially when in the control group that did not take alcohol, the risks are even higher than in moderate drinkers. This may be due, on the one hand, to serious diseases in which doctors completely prohibit alcohol, or these people used to be alcoholics and therefore stopped drinking. On the other hand, moderate alcohol consumption can be part of a healthier diet in general, like, for example, a glass of red wine in the Mediterranean diet. Which is also not evidence in favor of alcohol.
In 2018, the Lancet medical journal published a study according to which alcohol is certainly harmful to human health. According to its authors, the level of alcohol consumption, which minimizes health risks, is zero standard doses per week.
What is being investigated now: the most interesting
Now there are two main blocks of research that are being conducted in the field of prevention of cardiovascular diseases. The first is related to the use of bioinformatics methods to analyze an array of data including the results of genome sequencing. These are the results correlated with biomarkers, such as blood counts and the prognosis of patients, that is, the presence or absence of cardiovascular diseases. In addition, there is a very interesting point – the search for anti-risk factors that reduce the risk in patients with high traditional risk factors.
And the second direction is to unravel the immune mechanisms of the development of heart disease. Perhaps, in order to approach this, it is necessary to disassemble a bunch of mental factors, the role of stress, the immune system and the microflora affecting the immune system. Probably, having understood this bundle, we will better begin to realize the early stages of the development of cardiovascular diseases.
About the author: Yaroslav Ashikhmin – Candidate of Medical Sciences, therapist, cardiologist, Advisor to the Director General of the International Medical Cluster Foundation.
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