THE CHOLESTEROL CONTROVERSY

[First published in Art of Healing/Fit4Life on 13/10/2013]

IS HIGH CHOLESTEROL REALLY BAD?

An estimated one in three people above 40 are on anti-cholesterol drugs or some other cholesterol-lowering treatment. This is because about 40% of those above 40 have high cholesterol (total or “bad” cholesterol). For those above 50, it is probably over 50%. The current medical advice is to keep your cholesterol (especially the “bad” LDL-cholesterol, LDL-C) within normal range to avoid heart disease. For those with high risk (eg. diabetics) or already have heart disease, the medical management is to keep the total and LDL-C as low as possible.

The debate begins with whether high cholesterol is really an important risk factor for heart disease? The second question is whether reducing cholesterol using statins reduces the risk of heart disease? The third is whether using statins to reduce cholesterol reduces deaths from heart disease and deaths from all causes? Finally, overall, is the use of statins justifiable (benefits versus harm)?

Doctors have been fed with results of studies that affirm the belief that cholesterol is bad and reducing it improves the health outcome, and therefore convince them that anti-cholesterol drugs are necessary. Now that regulations have come out compelling drug companies to also release results of studies that are not in favour of their drugs, we are beginning to see a more balanced picture.

THE CHOLESTEROL CONUNDRUM

About two years ago, I wrote in Controlling Cholesterol (Fit4Life 20/11/2011): “While there is no doubt that many studies have shown the benefits of normalizing lipid levels (to reduce the risk of heart attacks, stroke and peripheral arterial disease), my concern is that most patients are put on the statin drugs without recourse to basic and safer alternatives first.”

Since then I have reviewed many reports and discussions on the subject and found that there are many doubts on the supposed benefits of lowering cholesterol levels, in particular the use of statin drugs to achieve that.

Some cardiologists and cardiac surgeons (eg. Dr Stephen Sinatra, author of The Cholesterol Myth) also query the fact that many patients with not-so-high cholesterol levels end up with serious blockage of their arteries, while others with high levels do not have serious disease. While we all know that heart disease has many contributing risk factors, so much focus has been on cholesterol and the use of statin drugs to lower it. That is why so many people are now on statins.

Most doctors now prescribe statins to their patients because of the convincing “evidence” presented to them over the last three decades. The standard model is that HDL-C is good for the heart, and LDL-C is bad. So when we say high cholesterol is bad, we mean high LDL-C, or high total cholesterol (Total-C) with a disproportionately high LDL-C component. The risk value of the different cholesterol types is expressed in the ratio Total-C/HDL-C. A value of 5 or more is considered high risk, and 4 or below is desirable.

According to WHO, a third of ischaemic heart disease is attributable to high cholesterol, and that a 10% reduction in serum cholesterol in men aged 40 reduces heart disease by 50% in 5 years.

So some doctors are so convinced of the benefits of statins that they prescribe them to almost all their adult patients. One such doctor is Dr Michael Miller, the director of the Center for Preventive Cardiology at the University of Maryland Medical Center. He tells his patients to regard statins like a daily vitamin boost because “it’s the only one that we know that works so well to improve cholesterol and lower cardiovascular risk” (reported in WedMD).

His view is echoed by Dr Patrick McBride, the director of the Cholesterol Clinic at the University of Wisconsin School of Medicine and Public Health. He said that “Statins are one of the great success stories of modern medicine” (reported in WebMD).

With such top experts endorsing the use of statins, how can it be wrong? Well, nobody disputes the fact that statins are very good at reducing cholesterol levels (never mind the side-effects). What is contentious is whether high cholesterol is really that bad; and whether reducing cholesterol levels lowers the cardiovascular risks and overall health outcomes as claimed.

Many doctors and researchers are now beginning to have a re-look at the role of cholesterol in cardiovascular disease, the necessity of reducing cholesterol levels, and the role of statins as the preferred treatment (in addition to diet and lifestyle modification) to lower cholesterol significantly because the “evidence” has now become shaky. Below are some examples of the contrary evidence (with references).

CHOLESTEROL LEVELS MAY NOT CORRELATE WITH HIGHER OVERALL DEATH RATES

 A study across 5 European countries reported in 2005 (European Jnl Epidemiology 2005, Volume 20, Issue 7, pp 597-604) showed a strong correlation between cholesterol levels and deaths from heart disease, but no correlation between cholesterol and stroke or overall deaths (ie. from all causes).

If the deaths from heart disease increase with higher cholesterol, but deaths from all causes do not, that means deaths from other causes decrease with higher cholesterol. What is most important is avoiding early death from all causes, not just from heart disease, as we have all this while been focused to.

The results imply that the higher cholesterol may be protective against other causes of death (eg. we now know that higher cholesterol means lower deaths from haemorrhagic stroke, but higher deaths from occlusive stroke such that overall there is no correlation between cholesterol levels and stroke deaths). The other top cause of death is cancer. Indeed some studies show that high cholesterol protects against cancer deaths. However, for studies which include men and women, a different conclusion may be arrived at if the data for men and women were studied separately (see Norwegian study below).

Another study across 15 countries (14 countries in Europe plus Australian Aboriginals) shows no correlation at all between cholesterol levels and heart disease. Lithuania, with average cholesterol level of about 6 (mmol/L) has the highest prevalence of heart disease, while Switzerland, with the highest average cholesterol of nearly 6.5 has the third lowest heart disease prevalence. France has the lowest heart disease rate, while the average cholesterol level was about 5.7 (the French paradox comes to mind). The most puzzling is when all this is compared with the Australian Aboriginals whose heart disease rate is almost double that of the Lithuanians. Their cholesterol level (4.9) is lower than that of all the Europeans! (European figures derived from WHO MONICA Project; Australian Aboriginal data is for same period of study, courtesy Dr Malcolm Kendrick, author of The Great Cholesterol Con).

Most other studies only compare the cholesterol - heart disease risk within a certain population, and when multiple populations were studied, the results were often lumped together. This cross-border comparison forces us to review the “direct” correlation previously taken for granted.

This shows not only that there are other factors contributing to heart disease, but also that some of these other factors are more important, such that they throw the cholesterol - heart disease connection into disarray.

LDL-C IS NOT A RELIABLE PREDICTOR OF HEART ATTACKS

Risks factors are valuable if they are reliable predictors of future disease. LDL-C has long been accepted as a risk factor for cardiovascular disease. So it would seem logical that lowering LDL-C should lower the risk. However, evidence-based medicine cannot be based just on expectations. Thus it comes as a surprise that although doctors have asked their patients to lower their LDL-C, so far no study has actually been done to prove that lowering LDL-C to the target level reduces heart disease.

A study on 100 heart attack victims had in fact shown that their LDL-C levels were the same as in the control group, which means LDL-C is not a good predictor of heart attacks. The better predictor was hsCRP (high-sensitivity C-reactive protein), which is a marker for inflammation (see Datta S, et al. Comparison between serum hsCRP and LDL cholesterol for search of a better predictor for ischaemic heart disease. Ind J Clin Biochem Apr-June 2011 26(2):210-213). I will elaborate more on the overlapping roles of inflammation and cholesterol in the etiology of heart disease in future articles.

A Harvard-led study had in fact shown that it is the triglycerides (TG, another type of fat routinely measured in the lipid-profile blood test), and not LDL-C, which is the worse promoter of heart disease. They measured the various ratios involving cholesterol and triglyceride and found that the most predictive of coronary artery disease is the TG/HDL-C ratio, and not the total-C/HDL-C ratio that is currently being used. The TG/HDL-C ratio does not include LDL-C at all (whereas it is included in the total-C/HDL-C ratio, since LDL-C is part of the total-C), thus again implying that the role of LDL-C as a risk factor has been exaggerated (see Circulation 1997; 96:2520-2525).

WOMEN BENEFIT FROM HIGHER CHOLESTEROL

The Norwegian HUNT 2 Study (J Eval Clin Prac 2012 Feb) followed 52,087 Norwegians aged 20-74 who were free of cardiovascular disease (CVD) at the start, for 10 years. The study assessed the relationship of total cholesterol with total mortality, CVD mortality, and heart disease mortality. It concluded that the cholesterol-risk profiles for men and women were totally different. Women in fact benefited from having higher cholesterol levels! See the chart below:

Risk of death from all causes in women is lower with higher Total-C (starting from about 4.6 mmol/L onwards), but increases for men (starting from about 5.3 mmol/L onwards).

The chart may also explain why when women and men are considered together, there is no correlation between high cholesterol and deaths from all causes. The reason is that when we separate the data of the men and women, we find that the risk rises for men, but reduces for women, and the two combined will cancel out.

Yet until now, millions of women continue to be prescribed statins as primary prevention, against the available evidence, to reduce their cholesterol when in fact studies showed lowering the cholesterol increases their risk. A Harvard study also showed that men above 69 also do not benefit from lowering their cholesterol (the studies will be reported in the next article). I hope our health care authorities take note of this “evidence-based” conclusion.

SO IS HIGH CHOLESTEROL BAD OR NOT?

I have presented evidences that go against the current teaching that high Total-C and LDL-C are such important risk factors for heart disease and that lowering them is imperative. This may confuse patients and doctors alike.

I hope that what I have presented proves that the current teaching about cholesterol and heart disease has not been totally truthful to evidence-based medicine, and doctors should re-examine their position. Cholesterol is not as bad as it has been made out to be. In fact studies show that high cholesterol may protect against deaths from heart disease and against other causes of deaths in women, and doctors should be more cautious in prescribing statins to them with the evidence presented. The bigger culprit in heart disease is inflammation (more about this in future articles).

For now, the evidence shows that for men, high cholesterol correlates with higher heart disease and deaths from heart disease. So, does that mean lowering cholesterol using statins in those with high levels reverses the risk? The answer is not that simple (see next article).

In general, women need not worry about having high cholesterol because they benefit from it. And if you are a woman on statins, you should talk to your doctor about going off it. You may be an exceptional case.

I welcome comments and rebuttals from doctors who prescribe statins to their women patients.

In the next article, I will address the issue of whether using statins to lower cholesterol is justified by evidence-based medicine.

DR AMIR FARID ISAHAK