"Bad" protein is worse than "bad" cholesterol
Standard blood tests in the near future may include a new position: lipoprotein (a). Studies show that high levels of this protein, which carries lipids and cholesterol, are associated with an increased risk of cardiovascular diseases. The amount of lipoprotein (a) in a person's blood largely depends on genetics. This level remains relatively stable throughout life, unlike "bad" cholesterol – low-density lipoproteins (LDL), which varies depending on diet and lifestyle.
Since the amount of lipoprotein (a) is genetically determined, in people with high levels it is hereditary (unregulated), and therefore they are at risk of heart and vascular diseases.
A drug has been created that targets lipoprotein(a). It blocks the body's ability to produce this protein, reducing its level in the blood by 80%. The study showed that the drug is safe.
Currently, a clinical study is being conducted on the effectiveness of a sharp decrease in the level of lipoprotein (a) in people who already have cardiovascular diseases to reduce the risk of heart attack and stroke.
Lipoprotein (a) consists of a fragment of LDL and a protein called apolipoprotein (a). The link between LDL and the risk of cardiovascular diseases has long been proven: a high level of LDL in the blood leads to its entry into the walls of the arteries and an inflammatory immune reaction that leads to thickening of the walls and narrowing of the lumen of the arteries.
However, there are people who keep LDL levels consistently low, but still experience heart attacks. Therefore, researchers are interested in lipoprotein (a) and its possible role in the progression of heart disease.
The LDL component is one of the reasons that the risk of cardiovascular diseases is higher with high levels of lipoprotein (a) in the blood. But the second component – apolipoprotein (a) – causes a stronger inflammatory reaction than LDL, accelerating the development of plaques in the walls of the arteries. In addition, apolipoprotein (a) is able to prevent the dissolution of clots in the blood.
Sotirios Tsimikas and his colleagues from the University of California, San Diego evaluated APO(a)-LRx, developed by the pharmaceutical company IonisPharmaceuticals, in a phase 2 clinical trial to determine its effectiveness and select the optimal therapeutic dose. The drug blocks the matrix RNA carrying genetic instructions for the production of the protein component lipoprotein (a).
The study involved 286 patients with cardiovascular diseases, whose lipoprotein (a) level was at least 60 milligrams per deciliter of blood. Epidemiological data indicate that people with a lipoprotein (a) level of 50-100 mg/dl have a moderate increase in the risk of cardiovascular diseases. At levels above 100 mg/dl, the risk is considered high. It is estimated that about 20% of the population have lipoprotein (a) levels above 50 mg/dl.
A high dose of APO(a)-LRx led to a decrease in the level of lipoprotein (a) in the study participants by an average of 80%.
Currently, participants are being recruited into Phase 3 of a clinical trial conducted by the pharmaceutical company Novartis Pharmaceuticals, the purpose of which is to find out whether the drug is an effective means of reducing the risk of heart attack and stroke. The researchers plan to test the drug or placebo for about four years on a large sample of more than 7,500 volunteers with cardiovascular diseases and lipoprotein (a) levels above 70 mg/dl.
If successful, studies of the effectiveness of APO(a)-LRx in patients with high levels of lipoprotein (a) for the prevention of cardiovascular diseases will be necessary.
Article by S. Tsimikas et al. Lipoprotein(a) reduction in persons with cardiovascular disease is published in NewEnglandJournalofMedicine.
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