Prevent atherosclerotic cardiovascular disease by controling blood lipids

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Prevent atherosclerotic cardiovascular disease by strictly controling the source: blood lipids

Prevent atherosclerotic cardiovascular disease by controling blood lipids.  Strictly manage blood lipids to prevent and treat atherosclerotic cardiovascular disease from the source

Abstract

Atherosclerotic lipoprotein abnormality is the cause or culprit of atherosclerotic cardiovascular disease (ASCVD). In order to fundamentally prevent ASCVD, it is very important to actively and carefully manage blood lipids. The application of drugs to lower cholesterol levels can significantly reduce the incidence and mortality of ASCVD.

Effective management of blood lipids requires joint intervention in multiple targets of lipoprotein metabolism. Therefore, the combined application of lipid-lowering drugs is the general trend. The advantage of the combined application of lipid-lowering drugs is to increase the rate of blood lipid control compliance and reduce the incidence of adverse drug reactions. Strict management of blood lipids throughout life will surely reduce the risk of individual ASCVD.

Atherosclerotic cardiovascular disease (ASCVD) has become the primary threat to healthy in many countries. Although coronary heart disease is more common in clinic, these diseases can also be manifested as ischemic stroke (cerebral infarction), chronic kidney disease and intermittent claudication.

The formation of atherosclerotic plaques in the arterial wall, which results in stenosis of the lumen, reduces or even blocks the blood supply to important organs, is the common basic pathological change of this kind of disease. A large number of scientific studies have repeatedly confirmed that dyslipidemia, especially low density lipoprotein cholesterol (low density lipoprotein cholesterol, LDL-C) elevation is the most important pathogenic risk factor for ASCVD [1].

The entry of atherosclerotic lipoproteins in the blood into the arterial wall is a necessary condition for the initial formation and progression of atherosclerotic plaques.

Although atherogenic lipoproteins are mainly low density lipoproteins (low density lipoproteins, LDL), they also include triglyceride-rich lipoproteins (TRL), such as very low density lipoproteins (very low density lipoproteins). density lipoprotein (VLDL), remnant lipoprotein (RL) and lipoprotein (a) [Lp (a)], etc. [1, 2].

These atherosclerotic lipoprotein abnormalities should be regarded as the cause of ASCVD or called the culprit [1], and other factors (risk factors) related to the occurrence of the disease, such as high blood pressure, diabetes, and smoking, are only accomplices.

Therefore, in order to fundamentally prevent ASCVD, it is very important to actively and conscientiously manage blood lipids [3].

1. Raise the public’s awareness of the dangers of dyslipidemia

At present, people’s understanding of the harm of abnormal blood lipids is still very insufficient, and there are even many misunderstandings. Compared with other cardiovascular disease risk factors, such as hypertension, which are easier to find and identify, the public’s awareness of dyslipidemia is low. Even some medical workers do not know that dyslipidemia is the most common cause of ASCVD such as coronary heart disease and cerebral infarction. The main pathogenic risk factors.

In recent years, many guidelines for the prevention and treatment of dyslipidemia have been published at home and abroad [3, 4, 5, 6, 7], and are constantly updated, but the blood lipid management methods recommended by these guidelines have not been clinically effective and extensive Applications.

It is a very important task to improve the awareness of dyslipidemia among the whole people and participate in blood lipid management together. In the past 40 years, with the reform and opening up, the life style of the people in our country has undergone tremendous changes, resulting in a significant increase in the blood lipid level of the whole people. Correspondingly, the incidence and mortality of coronary heart disease in our country have also increased significantly.

As early as the 1980s, 9 021 male and female subjects aged 35 to 65 years were followed up in Shanghai for 8 to 13 years. It was observed that the baseline total cholesterol level in the population was positively correlated with the death of coronary heart disease, and the total cholesterol increased every time. 10% (0.47 mmol/L), the risk of death from coronary heart disease increases by 23%, and this effect can be seen as long as the total cholesterol is >135 mg/dl (3.5 mmol/L).

An epidemiological survey of local residents was conducted in Beijing from 1985 to 1999. The results showed that during this period, the incidence of smoking, diabetes and hypertension among the population did not change much. The most obvious change was the total cholesterol level. An increase of 24%, while the death rate of coronary heart disease among these residents increased by 111%. Attribution analysis shows that among the factors leading to the increase in coronary heart disease mortality, the contribution rate of increased blood cholesterol is as high as 77%.

2. Good management of blood lipids can greatly reduce the risk of ASCVD

A large number of scientific research data confirms that lowering cholesterol levels can significantly reduce the incidence and mortality of ASCVD. Sweden analyzed the reasons for the decrease in mortality from coronary heart disease in the country from 1986 to 2002 and found that the decrease in cholesterol was the main reason for the decrease in coronary heart disease death (40%). Finland used to be one of the countries with the highest death rate from coronary heart disease in the world, as high as 450/100,000, especially in men. Beginning in 1972, Finland implemented the “North Carolina Health Promotion Project”, which reduced the per capita cholesterol level in Finland by about 20% and the death rate of coronary heart disease by 66%.

To manage blood lipids well, in addition to actively advocating a healthy lifestyle, starting the correct lipid-lowering drug treatment at the right time is the key. Statins are the most effective drugs for lowering cholesterol levels, especially LDL-C levels.

Regarding the evidence-based evidence for the benefit of lowering cholesterol in the prevention and treatment of coronary heart disease, the most milestone is the 5 large-scale clinical trials of statins. These clinical trials have confirmed that the application of statins can significantly reduce the blood cholesterol and LDL-C levels of patients, and significantly reduce the mortality of patients with coronary heart disease [6, 7].

The results of the meta-analysis showed that for every 39 mg/dl (1.0 mmol/L) reduction in LDL-C, the risk of major cardiovascular events was reduced by 20%, and the risk of major coronary events was reduced by 23%.

3.  focus on multiple targets to intervene in lipoprotein metabolism

The “magic curative effect” of statins that can significantly reduce the risk of ASCVD stems from the reduction of blood lipid levels, accompanied by the stabilization or even regression of atherosclerotic plaques.

Other drugs that can lower blood lipids, such as cholesterol absorption inhibitors, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, etc., have also been proven to have similar effects.

Therefore, as long as the level of atherogenic lipoprotein in the blood can be reduced, the risk of ASCVD can be reduced, regardless of the type of drug used.

Statins inhibit the rate-limiting enzyme of cholesterol synthesis in liver cells, reduce liver cholesterol synthesis, feedback up-regulate the expression of LDL receptors, and accelerate the elimination of LDL-C in the blood, becoming a good medicine for lowering cholesterol.

However, due to the complex metabolism of human blood lipids, there are many enzymes or receptors related to lipoprotein synthesis and decomposition, and statins that rely on a single target cannot completely solve all the problems of abnormal blood lipid metabolism.

Studies have found that when the synthesis of cholesterol in the liver is inhibited, a compensatory increase in intestinal cholesterol absorption will inevitably occur. At the same time, enzymes such as PCSK9 that hydrolyze LDL receptors will increase accordingly. Therefore, in order to effectively manage blood lipids, it is necessary to intervene in multiple targets in the process of lipoprotein metabolism.

4. The combined application of lipid-lowering drugs has become an inevitable trend

The effect of statins in lowering cholesterol is characterized by small doses, large effects, doubled doses, and little increase in lipid-lowering efficacy. This is also the limitation of statin monotherapy. Simply increasing the dose of statin does not significantly enhance its cholesterol-lowering effect, but increases the toxic side effects of the drug. Therefore, from the perspective of reducing the efficacy of LDL-C, it is a wise move to add other cholesterol-lowering drugs to the appropriate amount of statins.

The results of a number of large-scale clinical studies have repeatedly confirmed that the addition of cholesterol absorption inhibitor ezetimibe or PCSK9 inhibitors such as iloyuumab and alixiyuumab on the basis of statins can not only achieve better results Single use of high-dose statins to reduce the efficacy of LDL-C can also further reduce the cardiovascular risk of high-risk ASCVD patients, and more effectively improve the prognosis [5].

Therefore, for high-risk patients with ASCVD who cannot achieve the LDL-C treatment target value with statins alone, cannot tolerate them, or need to use high-dose statins, the combined application of multiple lipid-lowering drugs can achieve good clinical benefits. The advantage of the combined application of lipid-lowering drugs is to increase the rate of blood lipid control compliance and reduce the incidence of adverse drug reactions. Combined lipid-lowering drug treatment programs are mostly composed of statins and another or multiple lipid-lowering drugs with different mechanisms of action. For different types of dyslipidemia people, different lipid-lowering drug combined application programs can be implemented.

5. Adhere to early and long-term lipid-lowering treatment strategies

The pathological changes of atherosclerosis is a slow and long-term progression. Managing blood lipids early in life can more effectively prevent and reduce the risk of ASCVD. The results of genetic epidemiological studies have shown that for every 38.6 mg/dl (1 mmol/L) reduction in LDL-C, the risk of coronary heart disease can be reduced by 50% to 60%. The treatment benefit of lowering LDL-C from the early life is three times that of the treatment at the end of life.

The concept of cumulative LDL-C load believes that when the average person is 55 years old, if the cumulative LDL-C load is 160 mmol, it is enough to cause coronary heart disease.

Some patients with cholesterol metabolism disorders at birth, such as familial hypercholesterolemia (FH), if they are homozygous, will develop coronary heart disease at an early age (12.5 years old).

For patients with heterozygous FH, if they do not receive lipid-lowering treatment, their cumulative LDL-C load value can reach 160 mmol at the age of 35; if they receive lipid-lowering treatment from 18 years old, patients with heterozygous FH reach cumulative LDL -The age of C load value can be postponed to 48 years old; if treatment is started from 10 years old, it can be postponed to 53 years old, which is almost close to the average adult. Therefore, it is necessary to implement ultra-early diagnosis and ultra-early intervention for FH patients to prevent coronary heart disease.

The occurrence and development of atherosclerosis is a dynamic and balanced process, and whether an individual suffers from coronary heart disease or other ASCVD due to atherosclerosis depends on the positive and negative growth and decline of the two forces of forward development and reversal of the disease. [8].

The dialectical thinking of the mechanism of this disease has not only been confirmed by a large number of clinical trials, but also provided a positive concept for the prevention and treatment of ASCVD. From the perspective of the benefits of lipid-lowering treatment, long-term adherence to treatment is the most important.

For different individuals at risk of ASCVD, set LDL-C treatment target values, accurately evaluate the effectiveness of lipid-lowering treatment methods, and communicate and communicate effectively with patients to help them manage blood lipids strictly throughout their lives. Reduce the risk of ASCVD.

6. Comprehensive management of blood lipids is the direction of clinical exploration

Although by greatly reducing LDL-C or lowering LDL-C to a very low level, good results have been achieved, but there are still many ASCVD risks. Because atherosclerotic lipoproteins include VLDL, RL and Lp(a) in addition to LDL.

To further reduce the residual risk of ASCVD, it is necessary to actively reduce other atherosclerotic lipoproteins except LDL. Therefore, comprehensive management of blood lipids is the main direction of clinical exploration [2].

To fully manage blood lipids, it is necessary to add triglyceride-lowering drugs, such as fibrates or high-purity fish oil preparations, on the basis of statin treatment.

For patients with abnormally elevated Lp(a), it is also necessary to give corresponding drugs for intervention. In order to manage blood lipids more effectively and comprehensively, the questions that need to be solved in the future are: Who is the target population? When will it start? Which intervention plan to choose? Is it also necessary to set therapeutic target values ​​for all atherogenic lipoproteins? These are important topics that will be explored in the field of clinical blood lipids in the future.

(source:internet, reference only)

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