I recently had a family member ask for a bit of advice about cholesterol and I thought to myself that I would have a look at the current evidence for cholesterol-lowering advice and see if there is any new research or developments in this area.

What is cholesterol?

Cholesterol is a lipid produced by the liver and has many functions in our bodies, including maintaining cell structure, hormone production, vitamin D synthesis and bile production.[1]

Cholesterol travels through the bloodstream attached to a protein called lipoprotein.[1] There are different types of these lipoproteins, including HDL (high-density lipoprotein), which is often called ‘good cholesterol’ and LDL (low-density lipoprotein), which is known as ‘bad cholesterol.’[1,2]

HDL is beneficial, as it helps remove excess cholesterol from the blood and transports it back to the liver for processing.[1] LDL takes cholesterol from the liver to the cells.[1] High levels of LDL can lead to the build-up of plaques in the blood vessels (atherosclerosis) and increased risk of heart attack and stroke.[2,3]

Maintaining the right amount of lipoproteins in the body is important for long-term health. If a diagnosis of high cholesterol is made, there are medications and diet and lifestyle changes that will help reduce cholesterol levels and improve the ratio of HDL to LDL.

Dyslipidaemia and atherosclerosis

As well as HDL and LDL cholesterol measurements, research has shown that other components of lipoproteins, including VLDL, chylomicron remnants, IDL (intermediate density lipoprotein) and lipoprotein A, are significant, and their measurement helps calculate the risks of developing cardiovascular disease (CVD).[4] For example, lipoprotein A is a carrier of oxidised phospholipids. These are inflammatory and significantly increase the risk of developing atherosclerosis.[5] Atherosclerotic plaques cause arteries to narrow, thus limiting blood supply to vital organs. If a piece of plaque breaks off, it can cause a blood clot to form, completely blocking the blood supply to organs such as the heart or brain, leading to heart attack and/or stroke.[3]

Lifestyle and diet play a huge role in managing the risk of dyslipiaemia.[1] Other risk factors include:[6]

• Age
• Gender- (being male increases the risk of high cholesterol)
• Menopause
• Family history
• Kidney disease
• Liver disease
• Diabetes
• Hypothyroidism
• Growth hormone deficiency

Dyslipidaemia can occur secondary to other conditions such as diabetes and kidney disease, which is why cholesterol levels should be monitored for people with these conditions and treatment offered to reduce CVD risk if appropriate.[1]

High cholesterol is known as a silent killer, as there are usually no symptoms, so those affected have no way of knowing without a blood test. Those with familial hypercholesterolaemia (FH) may have some visible signs such as:[6]

• Tendon xanthoma: swellings on the knuckles or Achilles tendon from cholesterol deposits
• Xanthelasma: small yellow lumps in the corners of the eyes
• Corneal arcus: a white ring around the iris

It is thought that those with FH have an enhanced cholesterol absorption caused by certain gene variants in sterol transporters like ABCG5/G8 (estimated 30% of the population.)[7]

The NHS offers free cholesterol screening for those over 40 or for individuals with risk factors, i.e. family history of heart disease or hypercholesterolaemia, high blood pressure, diabetes and kidney disease.[8] The blood test checks levels of HDL, non-HDL, total cholesterol, the ratio of HDL to LDL and triglycerides.[9] Total cholesterol should be <5mmol/L, non-HDL <4mmol/L, HDL >1mmol/L and fasting triglycerides <1.7mmol/L.18. The primary targets for treatment are the total cholesterol and LDL levels, which have the greatest risk for developing CVD.[9]

Cardiovascular disease risk

CVD is the leading cause of death across the world and kills 17.9 million people (31% of all global deaths) each year.[11] CVD-related healthcare costs are around £7.4 billion per year.[10]

The good news is that there has been a fall in mortality rates from CVD from 2001-2016 in England, with increased life expectancy. However, since 2011, the mortality rates for CVD for both sexes have plateaued. This has led to a new drive for cholesterol and CVD research, enhanced screening and more targeted treatments for dyslipidaemia.[10]

The Q-Risk score is based on the number of risk factors someone has, e.g. family history, smoking and gender. The score shows the likely risk of developing CVD in the next 10 years.[11] Low risk is <10%, moderate risk 10-20% and high risk >20%.[11] The National Institute of Clinical Excellence (NICE) recommends that anyone scoring >10% should be offered counselling about treatment options for dyslipiaemia.[11] Diet and lifestyle changes are usually advised first for those with raised cholesterol and, if cholesterol remains elevated, medical treatment with statins will be offered. Statins are often started immediately in individuals who are very high risk: LDL >4mmol/l, high blood pressure, kidney disease, diabetes and previous heart attack.[12]

Statins

Statins have been a major breakthrough in preventing CVD deaths, and taking a daily statin reduces the risk of CVD by 25% even in those with a cholesterol <5mmol/L.[13] Statins work by blocking an enzyme called HMG-CoA Reductase, which in turn slows down the production of LDL cholesterol in the liver.[14] Statins can reduce your LDL cholesterol by 30-50% depending on the dosage.[14] However, like any medication, statins can cause side effects, the most common being headaches, nausea, fatigue, muscle pain, poor sleep and bowel problems.[12] There are also some more serious, rare side effects like low platelet count, pancreatitis and hepatitis.[12] There are five types of statins available on prescription in the UK at the moment:[12]

1. Atorvastatin (Lipitor)
2. Fluvastatin (Lescol)
3. Pravastatin (Lipostat)
4. Rosuvastatin (Crestor)
5. Simvastatin (Zocor)

For those who cannot tolerate statins there is an alternative cholesterol-lowering medication called Ezetimibe, which prevents cholesterol being absorbed from food.[15]

Cholesterol research

One of the most important CVD research trials took place in 2002 on over 20,000 people (known as the Heart Protection study) and it successfully showed that reducing levels of LDL cholesterol led to a reduced risk of heart attack and stroke and that statins were beneficial in the prevention of CVD.[3,13] This then underpinned the routine use of statins in primary care, to help lower people’s CVD risk.

The British Heart Foundation continues to help fund a lot of CVD research, and, on reviewing their website, I found there are many new areas currently being researched:

Gender reassignment and CVD risk

The risk of CVD may be higher in those who have undergone gender reassignment. Research from the University of Glasgow found trans women had an increased risk of heart attack and stroke compared with the rest of the population, and trans men were found to have higher blood pressure and cholesterol levels.[16] It is thought that there is a possible link between gender-affirming hormone therapy and the risk of blood clots and dyslipidaemia. However, research is still ongoing as the evidence base is not definitive.[16]

Tribbles-1
There is a protein known as Tribbles-1, which can reduce cholesterol levels, and with manipulation of microRNAs, the liver will produce more Tribbles-1, which will theoretically lower cholesterol. [17-19]

PET scans for diagnosis
Cambridge University is carrying out a study to look at improving the identification of atherosclerosis using positron emission tomography (PET) scans. It is hoped this method will help identify those who have large plaques in danger of rupturing, so preventative treatment can be given.[3]

Atherosclerosis
Cambridge University is also researching how blood vessels are affected by atherosclerosis and if it is possible to prevent this.[3]

Immune modulation
Genetic studies are being carried out focusing on the way T-lymphocytes react aggressively towards atherosclerosis, increasing damage to blood vessels. This may lead to an immune-modulating treatment that can reduce atherosclerotic damage.[3]

What about diet and lifestyle?

Many lifestyle interventions can help lower cholesterol and reduce the risk of CVD (and other health conditions), such as cutting down on alcohol, maintaining a healthy weight, exercising more and stopping smoking.[1,6,7,9,20] Foods that are high in cholesterol do not need to be avoided (such as eggs and prawns), but rather altering the profile of fats in the diet.[1]

A high intake of saturated fat can impact cholesterol as it reduces the liver’s ability to remove cholesterol.[1,21,22] Increasing dietary intake of polyunsaturated fat (Omega-3s called EPA and DHA) found in oily fish, nuts, seeds and green leafy vegetables has been shown to reduce the risk of CVD. [7,23] Having more wholegrains such as oats and barley is beneficial as they contain a soluble fibre known as beta-glucan, and this helps stop cholesterol being absorbed in the body.[24] Beta-glucan is also found in peas, beans and lentils, so a plant-based diet will have cardioprotective effects.[25] There is a relationship between glucose and lipid metabolism, and high carbohydrate diets have been shown to increase triglyceride levels.[9] Changing to lower glycaemic index carbohydrates, such as wholegrains, will help reduce the absorption of cholesterol.[9]

Sterols and stanols are naturally occurring plant-based compounds, and they have a chemical structure like cholesterol. There has been a huge amount of research into sterols and stanols, which has shown their efficacy and safety for cholesterol lowering.[25,26] Consuming around 2-2.5g a day from foods such as vegetable oils, nuts, grains and manufactured products with added sterols and stanols like margarine, yoghurts and milks, can help to lower cholesterol. (There are no further benefits from having more than 2.5g a day.)[26,]

Conclusion

Managing cholesterol levels is important for our cardiovascular health and there are clinically proven diet, and lifestyle changes we can make to achieve this. If diet and lifestyle changes are not enough however, then medications such as statins and Ezetimibe are effective at lowering cholesterol and reducing overall CVD risk. It is also encouraging to know that there are many research studies currently being carried out looking at more preventative treatments for dyslipidaemia and atherosclerosis which will hopefully save more lives in the future.