Going Beyond Cholesterol

Going Beyond Cholesterol

One subject that I am frequently asked about both by other doctors as well as patients is cholesterol. The topic of cholesterol is a source of huge debate and controversy in medicine at present. Sometimes the entrenched positions of the protagonists in this debate have resulted in unhelpful and confusing messages being delivered to the public. It’s particularly unhelpful when an incredibly nuanced subject is drilled down to a pithy one liner. So what is the truth about cholesterol? The truth is, it’s complicated.

The first thing to know about cholesterol is that it is very important, no crucial, for life. Each and every cell in our bodies is surrounded by a membrane made up of cholesterol. This cholesterol membrane is responsible for cell movement, transport of substances into and out of cells and for communications between cells. Cholesterol is also the building block for steroid hormones, including our sex hormones, such as oestrogen and testosterone.

One common misconception is that the cholesterol that we eat is solely responsible for our blood values of cholesterol. In fact, three quarters of the cholesterol in our bloodstream is made by our own bodies in the liver. Most of the cholesterol in our gut is cholesterol we have made, not cholesterol we have eaten.

“Good Cholesterol Gone Bad”

So if cholesterol is vital for our bodies how does it cause harm? Essentially cholesterol is “bad” for us when it enters the wall of our arteries. This may be our Coronary arteries where it may lead to heart disease or the carotid arteries in our necks where it can lead to strokes. Once inside the walls of our arteries the cholesterol attracts inflammatory cells causing a cascade of inflammation leading to unstable plaques that eventually cause the obstruction of an artery.

The key question is, how does this molecule that is so important for our bodies end up wreaking havoc in our arterial walls? Cholesterol can’t get into the artery wall on its’ own. It needs help to to this. The thing in our bodies that causes cholesterol to get into the walls of the artery is apolipoprotein B. Think of our artery as an important highway, lined with cool bars and clubs. The LDL cholesterol molecule wouldn’t normally be able to get into one of these bars, it needs something to help it gain entry. Apolipoproteins transport bundles of cholesterol and apolipoprotein B is like pulling up in front of a club in a brand new Ferrari. Usually this is enough the get past the bouncer on the door (in the body the role of the bouncer is played by Neimann-Pick C1-like 1 protein, NPC1P1; I told you it was complicated!). Once in the bar the LDL cholesterol starts shooting his mouth off and attracts group of cantankerous regulars (inflammatory cells in the body), a fracas ensues (inflammatory cascade), before the whole things spills out into the street attracting interested onlookers and blocking the flow of traffic and pedestrians (heart attack or stoke).

The greater the number of the LDL cholesterol molecules we have the greater the likelihood of them getting into the artery wall. However, this is not what is measured in traditional cholesterol readings which measure an estimation of the amount cholesterol per LDL rather than the number of LDL particles. The problem with this estimation is that it often does not tally either with the actual number of LDL particles, or the damage to the artery wall that LDL has caused. In fact, in a study of over 136,000 patients who were admitted to hospital with coronary artery disease in the USA almost half had a normal LDL concentration. What this suggests is that we need better ways than traditional cholesterol values at predicting who is likely to develop heart disease.

The Tests That Matter

One useful way to better predict risk of heart disease is to measure the number of molecules that assist the LDL cholesterol getting into our artery walls, the apolipoprotein b. A number of scientific studies have confirmed that measuring apolipoprotein b is superior to measuring LDL cholesterol (or non-HDL cholesterol as it is often called). In addition, a large number of organisations including the American Diabetes Association, the American College of Cardiology, the American Association of Clinical Endocrinology and the Canadian Cardiovascular Society support the use of apolipoprotein b not only to establish risk of cardiovascular disease but also to monitor how well treatments, be they lifestyle or medical, are working.

The way that LDL cholesterol causes damage in our arteries is by causing inflammation. So a recent way that doctors have tried to predict who is most at risk from heart disease and stroke is by measuring inflammatory proteins that are part of this inflammatory process. One such protein is called highly sensitive CRP or hs-CRP. Several big scientific studies have shown that people at the lowest risk of heart disease have both low LDL cholesterol and low hs-CRP.

The dangerous endpoint of the damage caused to the artery by LDL is when the collection of inflammation in the artery wall, known as a “plaque”, becomes unstable, and bursts. This causes a blood clot to form on the ruptured plaque as the artery tries to heal itself. Inevitably this clot breaks off causing a loss of blood supply to the heart downstream. Measuring the levels of one of the key players in making the plaque unstable can be very useful in finding out who is most at risk of getting heart disease. This key player is known as lipoprotein associated phospholipase (Lp-PLA2) and the test for it is called the PLAC test.

These tests for apolipoprotein b, Lp-PLA2 and hs-CRP are incredibly valuable for two reasons. Firstly, they can identify those people who are most at risk of heart disease and stroke therefore allowing effective lifestyle and medical treatment to be started. Secondly, it can also be used to identify patients who are at low risk and therefore do not need any medication to lower cholesterol. This could not only save on health expenditure but also reduce the side effects that taking medication brings.

So cholesterol level in the traditional sense is not the only factor involved in the development of heart disease. Not only that but knowing our cholesterol level provides only a small proportion of the information required for us to best discover who is most at risk of heart disease. To find this out, and reduce the epidemic of cardiovascular disease, we need to go beyond cholesterol.

Dr Hugh Coyne

Read more about Advanced Cardiac Blood Analysis available at Coyne Medical.