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.

Saturated fats, dairy foods and health: A curious paradox?

“…Recent meta-analyses of prospective studies (Siri-Tarino et al 2010;Chowdhury et al 2014;de Souza et al 2015) have raised doubts about whether a high intake of SFA is a risk factor for CVD. The specific effect of SFA on CVD risk is well established and is mainly mediated via increases in blood lipids, particularly low-density lipoprotein cholesterol (LDL-C) (Griffin 2017). There is strong evidence implicating LDL-C as a risk factor in CVD events (Ridker 2014) and randomised controlled trials (RCT) with LDL-C lowering interventions have confirmed a causal relationship between blood LDL-C and CVD, particularly coronary heart disease (CHD; Marz et al 2016).…”

The big fat debate

“…Ecological evidence from the 1950-90s, such as the 16 cohorts included in the Seven Countries Study, correlated average population SFA intakes, serum cholesterol levels and coronary heart disease (CHD) mortality (Keys et al 1986;Griffin 2017). Such strong associations have been over-simplistically extrapolated to infer reduced CVD mortality is associated with lower SFA intakes, which forms the basis of global dietary recommendations aimed at reducing the CVD burden.…”

Draft reports from the UK's Scientific Advisory Committee on Nutrition and World Health Organization concur in endorsing the dietary guideline to restrict intake of saturated fat

“…This point is, that the strength of the relationship between SFA and the development and clinical endpoints of CVD, and underlying foundation of the dietary guideline, rests largely on the capacity of SFA to raise serum low density lipoprotein (LDL) cholesterol. SFA and CVD are not linked directly by a straight line but by a triangle, two sides of which are supported by irrefutable evidence that LDL is a causal risk factor for the development of atherosclerosis (The ‘Cholesterol or lipid hypothesis’, reviewed by Griffin ) and that certain SFA raise serum LDL‐cholesterol (Fig. ).…”