There are also other types of cholesterol which, together with LDL-C, are associated with long-term risk of atherosclerotic CVD (ASCVD).⁷ These are collectively known as non-high-density lipoprotein cholesterol (non-HDL-C). Assessment of non-­HDL-C (total cholesterol minus HDL-C) is recommended by current US and European guidelines for cardiovascular risk estimation independently of LDL-C.^8,9

Plant stanol ester has been shown to reduce non-HDL-C at similar levels to LDL-C when consumed at a 2–3 g per day intake of plant stanols.^10–14

A recent study by Gylling et al. showed that plant stanol ester reduces LDL-C dose-dependently and, based on surrogate estimates, such LDL-C lowering reduces the risk of ASCVD events dose-dependently (ASCVD events are major vascular events, comprising fatal or non-fatal coronary artery disease, coronary artery revascularisation, or stroke). These novel estimations demonstrated that a consumption of 2 g/day plant stanols reduced LDL-C concentrations by 0.33 mmol/L, which was expected to reduce the risk of ASCVD events by 6.9%. For consumption of 3 g/day plant stanol, the respective estimates were –0.42 mmol/L and –8.8% (see table below).¹⁵ Based on EU guidance, consumers are not recommended to have a >3 g/day intake of plant stanols.

Change in LDL-C concentrations by plant stanol ester consumption and its predicted impact on the risk of ASCVD events*¹⁵

*ASCVD events = major vascular events (fatal or non-fatal coronary artery disease, coronary artery revascularisation, or stroke).

Some of these risk factors can be managed, such as a poor diet or physical inactivity, while others are not modifiable, such as genetic factors and ageing. Fortunately, 80% of premature heart attacks and strokes are preventable with careful management of modifiable risk factors.¹⁶

Elevated blood cholesterol, or hyperlipidaemia, is a major modifiable risk factor for CHD and widely studied. LDL-C in particular has been directly implicated in the development of ASCVD.¹⁷

Millions of people around the world live with elevated cholesterol, and according to the World Health Organization, a third of global CHD is attributable to high cholesterol alone.³ It is estimated that raised cholesterol causes 2.6 million deaths and around 30 million disability-adjusted life years globally.³

It is well established that lowering LDL-C decreases the number and risk of coronary events.^4–6

LDL cholesterol: the earlier the better, the lower the better

There is good evidence to indicate that the process of atherosclerosis can manifest before there are any apparent risk factors. A 2017 study of 1,779 subjects who did not exhibit CVD risk factors found that plaque or coronary calcification were present in 49.7% of these subjects.¹⁸

The findings suggest that many middle-aged people with an LDL-C concentration greater than 50–60 mg/dL (1.3–1.6 mmol/L) may already have clinically manifested atherosclerosis,¹⁸ even though these concentrations are currently considered as normal according to clinical thresholds. This supports the case for more effective LDL-C lowering, even in individuals without conventional cardiovascular risk factors.

A series of meta-analyses by Ference et al. have shown that a life-long low LDL-C level reduces the risk of CHD substantially more than lowering LDL-C later in life. Long-term exposure to lower blood LDL-C due to certain gene variants resulting in lower LDL-C levels was associated with a 54.5% reduction in the risk of CHD for each mmol/L lower LDL-C.¹⁹ The study provides strong evidence for a prophylactic approach to lower the risk of CHD by lowering LDL-C earlier in life, for example via lifestyle adjustment.

In addition, during the 85th European Atherosclerosis Society (EAS) congress, the EAS published a consensus statement which states that the effect of LDL-C is cumulative, meaning that the higher the LDL-C is and the longer a person has elevated LDL-C, the higher the risk of ASCVD.¹⁷ Thus, lowering LDL-C early in life provides a major opportunity to reduce the lifetime risk of a cardiovascular event.

Even small LDL cholesterol reductions can make a difference 

The well-established linear relationship between LDL-C and relative risk of CHD has been consistently supported by clinical, epidemiological and genetic studies.^17,20,21 It suggests that even small LDL-C reductions are worthwhile to minimise risk of disease and that an additional reduction in CHD risk is obtained when LDL-C is reduced below the typically recommended upper LDL-C concentration of 110 mg/dL (3.0 mmol/L).

Linear association between LDL-C level and absolute CHD event rate based on the extensive clinical evidence. Trend lines for primary and secondary prevention associations are virtually superimposable.
Adapted from Ference et al. 2017.¹⁷
CHD=coronary heart disease; LDL-C=low-density lipoprotein cholesterol.

The data suggest that for every 10 mg/dL (0.26 mmol/L) decrease in LDL-C, the relative risk for CHD is reduced by approximately 10%.¹⁷

The IMPROVE-IT study provides strong evidence that lowering LDL-C through the reduction of cholesterol absorption from the digestive tract results in an expected reduction in the risk of major vascular events.⁶