What We Have Learned About Reducing Low-Density Lipoprotein Cholesterol and Coronary Plaques

After the introduction of statins in 1987 and the publication of the landmark Scandinavian Simvastatin Survival Trial in 1996, extraordinarily robust evidence has accumulated demonstrating that lowering levels of low-density lipoprotein cholesterol (LDL-C) is associated with a major reduction in cardiovascular morbidity and mortality. Determining how the reduction in LDL-C results in these benefits has been the subject of intense scientific interest during the last 4 decades. Initial efforts to answer this question focused on the possibility that statins might reduce the severity of coronary lesions, a logical and appealing hypothesis. Pioneering work by Brown et al using a cumbersome manual technique known as quantitative coronary angiography (QCA) suggested that reduction in lesion severity with pharmacological treatment might be possible. However, the focus on lesion severity assumed that coronary thrombotic events most commonly occur at sites with severe stenoses. Subsequently, provocative data suggested that coronary events do not most frequently occur at the site of severe stenoses, instead often occurring at lesions that would be deemed clinically insignificant.