What is the optimal LDL cholesterol level for patients with cardiovascular disease?

High blood pressure in low-density lipoprotein cholesterol (LDL-C) is a major causative factor in coronary heart disease. Lowering LDL levels with medicine and / or diet is known to reduce the risk of cardiovascular disease.The effectiveness of low LDL levels in reducing the risk of vascular events in atherosclerosis is discussed in a recently published article in the journal. North American Endocrinology and Metabolism Clinic..

Background

Hypercholesterolemia is a condition characterized by very high levels of LDL in the blood. Because LDL accumulates in the arterial wall, it is considered “bad” cholesterol and causes arterial narrowing and hardening, as well as obstruction of blood flow. Initially, blood cholesterol levels of 300 mg / dL were considered the upper limit of normal based on demographics.

Almost all mammalian nucleated cells can synthesize cholesterol, and LDL is only needed to recycle it. Newborn humans have very low levels of LDL compared to infants and adults. The large amount of cholesterol required for fetal brain development is synthesized in the brain.

Diseases caused by LDL receptor mutations, such as familial hypercholesterolemia, can significantly increase blood LDL levels, leading to the development of myocardial infarction and other atherosclerosis.

The effectiveness of lowering blood LDL levels in reducing the risk of coronary heart disease was first discussed at the 1984 National Institutes of Health (NIH) consensus conference. In 1987, the first statin drug, lovastatin, was introduced to the market.Showed important Effectiveness For controlling blood LDL levels. Since then, many highly effective cholesterol-lowering drugs have been developed, including atorvastatin, rosuvastatin, and ezetimibe.

Most cholesterol-lowering drugs have been shown to be highly effective in lowering blood LDL levels, which reduces the risk of myocardial infarction, stroke, and other atherosclerosis. Treatment with monoclonal antibodies targeting PCSK9 (liver protease) (alirocumab and evolocumab) in combination with statins has been shown to reduce LDL levels by 50%.

According to current European guidelines, a blood LDL level of 40 mg / dL is considered the target threshold for treating patients with two or more major atherosclerosis.

Cholesterol-lowering drug safety profile

The backbone of cholesterol-lowering therapy, statins are associated with several harmful side effects, including muscle damage and newly developed diabetes. However, there is ample evidence that muscle symptoms associated with statin treatment develop due to the nosebo effect, a negative treatment outcome resulting from patient distrust of treatment.

Treatment with alirocumab for more than 6 months has been shown to reduce LDL levels to less than 15 mg / dL without causing serious adversity such as cognitive impairment, newly developed diabetes, and hemorrhagic stroke. .. Similar results have been observed with evolocumab treatment.

An 80% to 90% reduction in PCSK9 blood levels via Inclisiran (siRNA) has been shown to reduce LDL levels by 50% without causing serious side effects. Taken together, these observations show that the ultra-low levels of LDL achieved by cholesterol-lowering therapy are not associated with major health hazards.

Usefulness of ultra-low LDL levels

Many clinical trials have been conducted to investigate the effects of lower LDL levels on reducing cardiovascular risk. According to these studies, the risk of cardiovascular events can be reduced by 22% per 1 mmol / L reduction in LDL levels. Blood LDL levels of 25-50 mg / dL are considered optimal for patients with atherosclerosis. However, it has been observed that lowering LDL levels below 25 mg / dL has no additional therapeutic effect on these patients.

Based on the available evidence collected from large cardiovascular outcome clinical trials, LDL levels below 40 mg / dL are believed to be beneficial in significantly reducing the risk of cardiovascular events. increase.

Highlighted observations

Based on the results of large clinical trials, the current article highlights two key points. Blood LDL levels below 40 mg / dL are set as the target threshold for cholesterol-lowering drugs in patients with two or more atherosclerosis.

No adverse side effects have been reported for LDL levels of 25 mg / dL, but further lowering of LDL levels may not bring additional benefits to patients with cardiovascular disease.