High cholesterol: introduction

Cholesterol is a fatty substance essential for normal body functioning. Higher levels of cholesterol in the blood are associated with an increased risk of coronary heart disease (CHD), stroke and peripheral arterial disease. The Global Burden of Disease project has estimated that in 2015 high total cholesterol accounted for 4.3 million deaths globally and the loss of 88.7 million disability adjusted life years (Forouzanfar, 2016). Globally, the burden attributable to high total cholesterol is increasing, probably because of ageing populations and westernisation of traditional diets, though the trend is in the opposite direction in high income countries.

There is some evidence that decreasing levels of cholesterol below those currently considered ‘normal’ would further reduce the risk of CHD and stroke. Introduction of new guidelines from the Scottish Intercollegiate Guidelines Network (SIGN) in 1999 reduced the threshold for 'raised cholesterol' in the UK from a total cholesterol level of 6.5 mmol/l to 5.0 mmol/l. The consensus in the UK is that 5.0 mmol/l is the point at which the total cholesterol level becomes 'raised'. Of note, however, a report from the World Health Organization has defined non-optimal cholesterol as having a mean cholesterol of >3.8 mmol/l (Lawes et al, 2004) and the global burden of disease study selected a theoretical optimal level for total cholesterol of 2.78-3.38 mmol/L. However in terms of delivering care for patients there has been a move away from focusing on cholesterol levels on their own towards assessing global cardiovascular risk.

The Scottish Intercollegiate Guidelines Network (SIGN) have published a number of guidelines that include discussion of high cholesterol.  SIGN 149 was published in 2017 and provides guidance on risk estimation and prevention of cardiovascular disease, including high cholesterol as just one of the risk factors considered.

Cholesterol is transported in the blood bound to lipoproteins, of which there are two broad types:

1. High density lipoprotein (HDL) is thought to transport cholesterol away from tissues and arteries and into the liver, and a high level in the blood is therefore protective against diseases of the heart and arteries. Cholesterol in this form is known as 'good' cholesterol.
2. Low density lipoprotein (LDL) is thought to have the opposite function, and cholesterol in this form is thought of as 'bad'.

Whilst this distinction is important, LDL makes up 60-70% of total blood cholesterol, and it is total cholesterol which is considered in this section of the website.

There are a number of different ways in which cholesterol levels in the blood can be measured; and the associated cardiovascular risk assessed. Blood measurements may consider HDL or LDL in isolation, the relative proportions of HDL and LDL or total blood cholesterol. In routine clinical practice LDL levels are usually estimated from total cholesterol, HDL and triglyceride levels using the Friedewald formula.