Genetically Determined Cholesterol Unresponsive to Statins May Triple Heart Attack Risk

A new class of cholesterol-lowering pills, recently approved in the US, targets LDL cholesterol but does not affect a specific, genetically determined type known as lipoprotein(a), or Lp(a). Cardiologists are increasingly concerned about Lp(a) because elevated levels, which are largely inherited, can triple the risk of heart attack. Approximately 20% of the population has high Lp(a) levels, often without realizing it, as it is not influenced by diet or exercise. Unlike LDL cholesterol, Lp(a) levels are primarily determined by genetics, with about 90% of a person's value stemming from heredity. High Lp(a), defined as levels above approximately 50 mg/dL, is also associated with aortic valve calcification. Medical guidelines, including those from the American College of Cardiology and American Heart Association, now recommend that all adults be tested for Lp(a) at least once in their lifetime. While there is no current medication to directly lower Lp(a), knowing one's level serves as a crucial warning to rigorously manage other cardiovascular risk factors such as LDL, triglycerides, blood pressure, and blood sugar. The development of specific treatments for Lp(a) is on the horizon, with Novartis's pelacarseno showing promising results in early studies by reducing Lp(a) by about 80%. The Horizon study is currently investigating whether lowering Lp(a) translates into a reduction in heart attacks and strokes, with results anticipated in late 2026. Cardiologists emphasize that while reducing Lp(a) is likely beneficial, definitive proof from long-term studies demonstrating a decrease in cardiovascular events is still pending.