Lowering LDL—Not Only How Low, But How Long?

摘要

The causal relation between plasma low-density lipoprotein (LDL) cholesterol (LDL-C) levels and coronary heart disease is well established. Compelling evidence from between-country comparisons shows that large and lifelong diet-related differences inLDL-C levels are associated with 10-fold differences in coronary mortality (1) (see the figure). Strong support comes from observations on genetic diseases such as heterozygous familial hypercholesterolemia, in which mutations in the LDL receptor gene double LDL-C levels throughout life and increase the risk of early heart attack by more than 10-fold (2). So, it has been somewhat disappointing that treatment with cholesterol-lowering statins for 5 years reduces the incidence of heart attacks by only 40%, even when LDL-C concentration is reduced by 80 mg/dl (3), a reduction that should give much more protection based on the population studies. A likely explanation is provided by Cohen, Hobbs, and their colleagues in this week's issue of the New EnglandJournal of Medicine (4). In lowering LDL levels, the appropriate consideration may be not only how low, but also how long.