Serum low-density lipoprotein as a dietary responsive biomarker of cardiovascular disease risk: Consensus and confusion

Abstract

The replacement of saturated fatty acids (SFA) has been the mainstay of our dietary guidelines to help prevent cardiovascular disease (CVD) for over 30 years. However, the underlying evidence to support this guideline is now held in contentious disrepute on the grounds of an apparent lack of evidence, largely from meta-analyses, for a direct relationship between saturated fat and CVD mortality. This can be explained by the fact that the relationship between dietary SFA and CVD is not direct, but indirect and mediated through the low-density lipoprotein cholesterol (LDL-C) raising effects of certain SFA, in certain foods. There is over 100 years of evidence to link raised serum cholesterol with CVD and to support the current consensus that serum LDL is causally related to CVD morbidity and mortality. Nevertheless, the role of LDL as a biomarker of CVD risk, as measured by its cholesterol content (LDL-C), is often confused with its contribution to cardio-metabolic risk by its conversion into small and dense LDL particles with increased potential to cause CVD. The clinical utility of serum LDL is outstanding as a biomarker for CVD, albeit through an increase in its cholesterol mass (LDL-C), its small particle size or over-abundance of these particles. What is of overriding importance is to identify and modify these characteristics in LDL at the earliest stage of their development and to reduce the associated CVD risk through appropriate and sustained changes in diet and lifestyle.