Julián Pérez-Villacastín
Head of Cardiology at San Carlos Clinical Hospital and professor at Complutense University of Madrid
High blood cholesterol is associated with an increased presence of atherosclerotic plaques in our arteries, particularly in the heart and brain. When these plaques rupture, a thrombus (blood clot) forms, blocking blood flow and triggering a heart attack. However, we know that total cholesterol consists of both "good," artery-protective particles—known as HDL—and "bad" particles—known as LDL—which not only promote the formation of plaques but also contribute to their rupture. Furthermore, numerous studies have shown that lowering LDL cholesterol levels—through lifestyle changes and medications such as statins—leads to a dramatic reduction in heart attacks.
Research has identified a lipoprotein known as lipoprotein(a), or Lp(a), which is structurally very similar to LDL particles. Individuals with higher levels of Lp(a) experience a greater number of heart attacks. Consequently, it has been recommended that everyone have their Lp(a) levels measured at least once in their lifetime. These levels are not influenced by diet or lifestyle; rather, they are genetically determined—we inherit them. It therefore seemed logical to assume that reducing Lp(a) levels would decrease cardiovascular complications, much as lowering "bad" LDL cholesterol has been shown to do.
However, this has not proven to be the case. The Lp(a)HORIZON study, which involved approximately 8,300 patients with established cardiovascular disease and elevated Lp(a) levels, yielded a negative result:
While the drug pelacarsen did successfully reduce Lp(a) levels, it failed to demonstrate a reduction in the incidence of heart attacks or strokes. A similar scenario occurred previously—though in the opposite direction—with "good" HDL cholesterol: while higher levels are generally considered beneficial, increasing them through medication did not improve patient outcomes.
Why, then, was a medication that effectively lowers Lp(a) not clinically efficacious in the studied population? At the moment, we do not know for sure, but one proposed explanation is that when Lp(a) levels are reduced later in life, the damage to the arteries has already occurred, which is why the expected benefits are not clearly observed. This aligns well with the concept that the prevention of atherosclerosis should begin much earlier—ideally, as early as childhood.
However, there remains the possibility that this lipoprotein is not as significant a driver of vascular damage as we have previously believed. Regardless, I do believe it is advisable to have one’s Lp(a) levels measured at least once in a lifetime. For individuals with elevated levels—much like those with a family history of cardiovascular disease or high cholesterol—such testing can help raise awareness that effective medications are now available, which can significantly improve both the length and quality of their lives. Ultimately, it is crucial to remember that the majority of our health depends on us and the lifestyle we choose to lead—and this is not something we can afford to put off until we are older.