The Cumulative Burden of Lipoprotein Cholesterol (LDL-C)

The discussion begins with a foundational review of the role of low-density lipoprotein (LDL) cholesterol in atherosclerotic cardiovascular disease (ASCVD) and acute coronary syndrome. Lowering LDL cholesterol is emphasized as the cornerstone of both primary and secondary prevention efforts. The cumulative exposure to elevated LDL, measured over a lifetime, directly influences the risk of cardiovascular events. This concept of “LDL burden” helps clarify why early and sustained lipid control is so critical in reducing long-term risk.

Gulati highlights contrasting examples to illustrate this principle. Patients with homozygous familial hypercholesterolemia, who experience extremely high LDL levels from a young age, often suffer from premature cardiovascular events. Conversely, individuals with naturally low LDL levels throughout life have a significantly reduced incidence of ASCVD. These data reinforce the idea that both the level and duration of LDL exposure are key determinants of cardiovascular outcomes.

As such, the discussion sets the stage for the rationale behind aggressive LDL-lowering strategies, especially early in life or immediately following a cardiovascular event. The cumulative evidence supports not just reaching LDL targets but doing so as early as possible and maintaining those levels over time. This approach underpins new therapeutic strategies, including using agents like inclisiran, that can reduce both LDL levels and the disease burden across a patient’s life span.