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Cholesterol screening and the Gold EffectAlison Hanna; Stephen Peckhamb

a School of Health Science, University of Swansea, UK b Department of Public Health Policy, LondonSchool of Hygiene and Tropical Medicine, UK

Online publication date: 05 March 2010

To cite this Article Hann, Alison and Peckham, Stephen(2010) 'Cholesterol screening and the Gold Effect', Health, Risk &Society, 12: 1, 33 — 50To link to this Article: DOI: 10.1080/13698570903499608URL: http://dx.doi.org/10.1080/13698570903499608

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Cholesterol screening and the Gold Effect

Alison Hanna* and Stephen Peckhamb

aSchool of Health Science, University of Swansea, UK; bDepartment of Public Health Policy,London School of Hygiene and Tropical Medicine, UK

(Received 5 December 2008; final version received 9 November 2009)

This paper explores the concept of the ‘Gold Effect’ in relation to the use of serumcholesterol measurement as a screening test for cardiovascular disease. The GoldEffect explains the phenomenon of the process by which an idea comes to be heldas a generally accepted truth. In this paper we argue that cholesterol screening isthe product of the Gold Effect. Screening tests need to be sufficiently robust as anindicator of risk and thus their evidence base should be clear and uncontested.While there has been a long standing debate about the link between highcholesterol and cardiovascular disease and, in particular, the use of statins as themain approach to lowering cholesterol levels, serum cholesterol measurement andlowering levels of cholesterol are widely accepted as NHS interventions and arefinancially incentivised. We start by discussing what cholesterol is and how it isscreened for in the UK. We then go on to examine the evidence for usingcholesterol as a risk marker for cardiovascular disease. We then discuss theresearch on reducing cholesterol levels through diet and by using statins. Wefinish by discussing the implications of this analysis and questioning whycholesterol is routinely screened for and why so much emphasis is placed oncholesterol reduction arguing that at the root of this approach there is amisconception about the relationship between fat and cholesterol and about therole of cholesterol in cardiovascular disease.

Keywords: public health; risk; evidence; screening

Introduction

It was just after this adventure that we encountered a continent of immense extent and ofprodigious solidity, but which, nevertheless, was supported upon the back of a sky blue cowthat had no fewer than four hundred horns. ‘That, now, I believe’ said the King ‘because Ihave read something of the kind before in a book’. Edgar Allan Poe

Over the past two decades there has been an increasing emphasis placed on

screening for high cholesterol and adopting interventions to reduce cholesterol levels

in order to reduce the risk of heart disease. In the UK there are specific targets for

cholesterol levels and a huge emphasis on reducing high cholesterol levels, which is

done either through dietary advice (usually avoiding saturated fat) or through the

prescribing of statins, which are a group of drugs with a strong cholesterol lowering

effect such as simvastatin or fluvastatin. The focus on cholesterol is likely to increase

in future as the NHS rolls out routine health checks for people aged between 40 and

*Corresponding author. Email: A.P.Hann@swansea.ac.uk

Health, Risk & Society

Vol. 12, No. 1, February 2010, 33–50

ISSN 1369-8575 print/ISSN 1469-8331 online

� 2010 Taylor & Francis

DOI: 10.1080/13698570903499608

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74 which includes screening for cholesterol. In this paper we examine the evidence

base for cholesterol screening and challenge the assumption that screening for

cholesterol will lead to reductions in heart disease. There are a number of problems

concerning the links between cholesterol and health risk and also in the relationship

between the reduction of cholesterol levels and consequent morbidity and mortality.

We argue that the focus on cholesterol may be misplaced as it is the result of the

‘Gold Effect’ where particular interventions build a momentum that does not relate

to the evidence on effectiveness. We start by outlining the nature of the Gold Effect

and then go on to examine the complex relationship between diet (especially

saturated fat), cholesterol and heart disease.

The relationship, between dietary fat, cholesterol and heart disease is complicated

because the argument contains three independent propositions, which contain a

number of assumptions: first, that lowering cholesterol prevents heart disease; second,

that eating less fat (or less saturated fat) not only lowers cholesterol but also prevents

heart disease, but third, that it prolongs life. In simple terms therefore, it is assumed

that screening for cholesterol (and controlling levels) prevent cardiovascular disease

and will prolong life. This orthodoxy has had important consequences for clinical

practice as GPs are encouraged to screen ‘healthy’ patients on an opportunistic basis,

and to meet their targets in order to meet quality thresholds for screening and, as a

result, trigger financial payments. However, as we argue in this paper, the relationship

is complex. High cholesterol has been identified as a risk marker, but may not be

associated with higher mortality from heart disease in all groups. Furthermore,

reducing cholesterol through dietary modification is not only difficult but there is

evidence that it may give rise to increased morbidity and mortality from other causes

(Dawber 1980, Stamler et al. 1986, Taylor 1987, Browner 1991). While statins reduce

cholesterol and provide benefits for some people they may also increase morbidity and

mortality due to their well recognised adverse effects (Colpo 2006). It is this complex

relationship that we examine in more detail in the following sections.

Cholesterol is not a disease or condition in itself, but relatively high levels of ‘bad’

cholesterol have been labelled as a risk factor for cardiovascular disease and, over

time, health systems do come to treat risk factors as if they have adverse outcomes in

their own right. At present it is generally believed, by many medical practitioners,

and other health professionals (as well as the lay public), that a high level of

cholesterol should be reduced to prevent the development of heart disease. In order

to unravel the evidence upon which this assumption is based, we need to first look at

some common misconceptions concerning the nature of cholesterol and its

relationship to diet and the development of cardiovascular disease. Then we

examine the evidence regarding the relationship between cholesterol levels and heart

disease and the impact on morbidity and mortality of using statins and diet to reduce

cholesterol levels.

The Gold Effect

The so called Gold Effect (named after its creator Professor T. Gold) was outlined by

Lyttleton (1979) who describes a process by which an idea comes to be held as a

generally accepted truth. In short, the process begins with a small group of

likeminded people who meet to discuss their idea. Next, those who have conceived

the idea decide to have a conference or meeting and at this meeting there will be more

people favouring the idea than against it. Then, a representative committee might be

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selected to publish a collection of papers and articles to foster interest in the idea.

The resulting articles and papers will show an increasing consensus of agreement and

the idea will gather pace and momentum. One of the aspects of the Gold Effect which

is important here, is that the pace at which such an idea can grow is assisted if the

idea links in with pre-existing beliefs or assumptions. For example, if there is already

a commonplace belief that being obese is bad for your health (and undesirable in

other more social ways), research which seems to suggest that obesity might be

linked to other diseases or risk factors is likely to attract medical and media

attention, and will be incorporated in to the ‘obesity is bad’ discourse which

reinforces the orthodox position both within the healthcare ‘establishment’, and,

importantly in the over the counter drugs industry and food manufacturers who will

use the ‘obesity is bad’ discourse to market food (and food supplements) which claim

to help you stay slim. The Gold Effect ensures that these mutually reinforcing

messages are rarely questioned or challenged. People who might have opposing

views find it difficult to get their views published, and are regarded as being

misguided or just plain wrong. As Lyttleton remarked, by this stage: ‘the idea is well

on its way to becoming something akin to a religion with a following of devout

believers’ (Lyttleton 1979, p. 189).

In the case of cholesterol and its association with heart disease, the prime mover

in the genesis of the anti-cholesterol ‘movement’ was undoubtedly Ancel Keys who

was one of the first to propose that saturated fat and cholesterol were responsible for

the widespread prevalence of heart disease in the developed world, though his

hypothesis remained controversial until a consensus conference in 1985 which was

hosted by the National Institutes of Health (1985). This was a watershed because the

consensus conference (chaired and organised by proponents of the cholesterol/heart

disease idea) published a ‘consensus statement’ stating that lowering blood

cholesterol in the population would lower the risk of heart attacks and coronary

artery disease, and that they were going to launch a nationwide cholesterol education

plan. This came as quite a shock to several members of the conference, who later

independently published their view that the statement had been ‘premature’ and not

based on good evidence, or indeed a consensus (Ahrens 1985, Kolata 1985, Oliver

1985). Colpo (2006) refers to this as the ‘cholesterol coup’. The education

programme was duly launched in November 1985 and the National Cholesterol

Education Programme (NCEP) made front page news in Time magazine and the

media enthusiastically took up the story that cholesterol ‘caused’ heart disease, and

that there was ‘no doubt’ that cholesterol was ‘bad’. What is important here, from

the point of view of the Gold Effect, is that once a ‘critical mass’ of people is created,

this produces an almost irresistible force which feeds into research funding and

publishing, and quite literally drowns out those who challenge the new orthodoxy. In

a nutshell, what the Gold Effect claims is that a lie told often enough becomes the

truth, and having achieved this status becomes entrenched in (in this case) health

promotion discourse. This means that the thesis becomes commonplace knowledge,

even if the evidence to support it is not very robust.

The association between cholesterol and cardiovascular disease has certainly

become the generally accepted position, and has formed the basis of health policy on

cardiovascular disease in the UK and other countries. However, the usefulness of

cholesterol as a screening test has been contested right from the start (see for example

Texon 1989, Davey Smith et al. 1993, Ravnskov 2002). As Wald et al. (1999) explain,

‘Because serum cholesterol is an established risk factor for ischaemic heart disease, it

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was believed that it would be a useful screening test . . . This belief was unfounded’ (p.

319). For a risk factor to be a useful screening test, it must be strongly associated with

the disorder, and while a risk factor may have a strong association with a condition,

this does not necessarily make it a good screening test. As Wald et al. (1994, 1999)

point out, the fact that a strong risk factor can be a poor screening test is

counterintuitive. However, despite scepticism from certain quarters regarding the

usefulness of cholesterol as a screening test, it has become embedded within the health

promotion practices of GPs, and what is more it is financially incentivised through the

pay for performance element of the GP contract (Peckham and Hann 2008).

Cholesterol: The good, the bad, and screening

Cholesterol is most accurately defined as a sterol and is one of several fatlike sub-

stances that circulate through the blood and they are known collectively as lipids or

blood lipids, and these include free fatty acids and triglycerides. It is a waxy, water-

proof substance which is produced mainly in the liver, although smaller amounts are

produced in the intestines and other organs. It is especially important for the correct

functioning of nerve cells and the highest concentrations of cholesterol in the body

can be found in the brain and nervous system. Cholesterol also acts as an antioxidant,

protecting cell membranes from free radical damage. Cholesterol levels are monitored

and controlled in the body via a ‘negative feedback system’ whereby the liver increases

or decreases manufacture of cholesterol according to circulating levels. Cholesterol

does not circulate freely, it is transported around the body inside lipoproteins along

with other fats, but the type and quantity of cholesterol that is contained within any

lipoprotein varies. These lipoproteins have been broken down into further ‘sub-

groups’ based on their density and, of these, three have become commonly used.

These are low density lipoproteins (the ‘bad cholesterol’), high density lipoproteins

(‘good cholesterol’) and very low density lipoproteins (‘very bad’). Most of the

triglycerides in the blood are carried round in very low density lipoproteins and this is

why it is considered the worst form, but most of the cholesterol is carried in low

density lipoproteins. This, to some extent, has led to the common belief that there is

‘good’ and ‘bad’ cholesterol and that this is somehow related to ‘good’ (unsaturated)

or ‘bad’ (saturated) fats. This distinction is important though because of the emphasis

on screening for cholesterol and reducing cholesterol levels. Screening consists of a

blood test normally taken after fasting. There are three measurements:

Total cholesterol

This is the measurement that patients commonly receive when they go for a cholesterol

test, and it is reached by adding together low density lipoproteins levels, high density

lipoproteins levels and a few other lipoproteins. Although widely used the concept of

average cholesterol is contested about 6.1 mmol/1 (millimoles per litre). Anything above

7 mmol/l is considered high.

Good cholesterol

This is the high density lipoprotein which is considered to be ‘normal’ at about

1.3 mmol/l, and anything above that is considered to be healthy and good, while

anything below 0.9 mmol/l is considered to be very bad.

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Bad cholesterol

This is the low density lipoproteins. The average for this is about 3.5 mmol/l.

Anything above 4 mmol/l brings someone into the ‘treatment zone’. However it is

important to note, that it has been known for a long time that in healthy individuals,

the low density lipoproteins level remains stable so no matter what you eat and no

matter what happens to the high density lipoproteins (or very low density

lipoprotein) levels it remains the same. This does not mean it never changes, but

that the regulation system in the healthy body maintains a stable level though

smoking or being overweight can raise the level (Colpo 2006). To sum up, a very low

density lipoprotein (VLDL) is a lipoprotein, but it’s never called that. Low density

lipoprotein (LDV) is a lipoprotein but it’s called ‘bad’ cholesterol. High density

lipoprotein(HDL) is the smallest lipoprotein and is called ‘good’ cholesterol, even

though none of these are actually cholesterol. So when total cholesterol1 is measured,

there is no way of knowing how the cholesterol itself is apportioned in individual

lipoproteins. In fact screening for cholesterol (low density lipoproteins and high

density lipoproteins) is simply providing a measure of the ‘fat’, not cholesterol and

does not give an idea of the very low density lipoproteins level which is arguably the

most important (Kendrick 2007a). Yet, screening for cholesterol forms a key part of

primary care activity to reduce cardiovascular disease (heart attacks and strokes).

Current NHS guidance recommends that any adults from 40 years of age

upwards who have no history of cardiovascular disease or diabetes and who are not

already on treatment for blood pressure or lipids should be considered for

opportunistic risk assessment (using a standard risk calculator) in primary care.

For primary prevention, NICE guidelines recommend that ‘the threshold for statin

treatment is a 20% CVD [cardiovascular disease] ten year risk’ (NICE 2008, p. 12).

In addition there is an emphasis on secondary prevention in those individuals who

have established cardiovascular disease, including the modification of lipids (through

the prescribing of statins).

In the UK, general practice plays a key role in the primary and secondary

prevention of cardiovascular disease and since 2004 general medical practitioners

(GPs) have been rewarded financially for measuring cholesterol levels and for taking

action to reduce serum cholesterol levels in individuals with ‘high’ cholesterol

through the Quality and Outcomes Framework Commonly known as QOF

(Peckham and Hann 2008). The Quality and Outcomes Framework contains a

target for the screening of high risk patients with cardiovascular disease at a total

cholesterol level of 5 mmol/L but does not set an low density lipoproteins target.

This compares to the British Hypertension Society who have set a lower total target

of 4 mmol/L6 as well as a target low density lipoproteins-cholesterol of 2 mmol/L6.

Despite the requirement that the Quality and Outcomes Framework indicators are

supposed to be evidence-based, as mentioned above, cholesterol levels are not a

strong screening indicator for cardiovascular disease.

GPs are encouraged to not just screen patients but are rewarded financially,

through the Quality and Outcomes Framework, for taking measures to reduce

cholesterol levels below 5.0 mmol/l. The impact of the Quality and Outcomes

Framework, as a financial incentive, on GP activity is of concern (Kendrick 2007a).

While the current guidance on ‘Lipid Modification’ issued by NICE suggests that in

order to lower the risk of coronary heart disease patients should be offered lifestyle

advice (advised to eat a low [saturated] fat diet and eat 5 portions of fruit per day) the

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pressure to ensure that patients’ cholesterol levels are lowered has led to a steady

increase in the use of statins as a first line of prevention. Lifestyle advice can be ignored

where as drug therapies are more within the control of the medical practitioner and

reduce cholesterol levels to meet target levels contained in the guidelines and to meet

payment thresholds in the Quality and Outcomes Framework.

Payment thresholds for screening for cholesterol may also lead to adverse

behaviour changes leading to goal misplacement in which rule following (i.e.

achieving the threshold for payment by screening and controlling for cholesterol)

becomes the end rather than focusing on maximising patient care and outcomes

(Harrison and Smith 2004). This seems to be borne out in practice, illustrated by the

following experience of one GP: ‘Many patients coming to my clinics are taking

statins even if their baseline cholesterol is only just above normal and no account is

taken of any change in risk with age. It strikes me as absurd to be starting an 84 year

old patient on lipid lowering agents, but the protocol for lipid management seem to

have resulted in completely uncritical prescribing phenomenon, largely driven by

targets and without regard for common sense’ (Bamji 2008, p. 1782). The

introduction of four yearly health checks in the NHS is likely to lead to an increase

in statin prescription (Kmietowicz 2009). The health checks, which focus on

cardiovascular disease prevention, include opportunistic screening for cholesterol if

other risk factors are identified. It is expected that 2.25 million people will undergo

health checks each year and new previously undiagnosed ‘high cholesterol’ will be

found and statins prescribed leading to up to 4 million extra statin prescriptions each

year at a cost of £1.16 billion. Yet the Government’s national director for heart

disease, Professor Boyle, ‘. . . has acknowledged that statins do not benefit 99% of

people who take them for primary prevention’ (Smith 2009, p. 18).

The active screening of cholesterol levels in patients is based on the assumption

that cholesterol is an important risk factor for cardiovascular disease and that it is

measurable and controllable. However, this perpetuates a number of misconceptions

about the links between cholesterol, dietary fat and heart disease and also about

what is being measured.

Cholesterol as a risk factor for cardiovascular disease

The precise relationship between dietary fat (saturated or otherwise) lipoproteins

and cholesterol has been debated ever since it was discovered in the early 1950s

(Goffman and Young 1958). The central claim made regarding the link between

dietary fat, cholesterol levels and heart disease is that populations with the lowest

saturated fat consumption should have the lowest incidence of heart disease. This,

however, is not supported by epidemiological evidence as there are many anomalies

that cast doubt on this double thesis upon which screening is based (see for example

Mann et al. 1964, Bliss 1971, Colpo 2006, Allender et al. 2007, Kendrick 2007a,

Allender 2008a). Another misconception is that cholesterol clogs up arteries, like

soot in a chimney, but this is also inaccurate2.

The assumed link between high levels of cholesterol and cardiovascular disease

has been challenged by a number of studies. For example, Sachdeva et al. (2009)

found that patients admitted to hospital with coronary artery disease had an low

density lipoprotein measurement of 2.7 mmol/l, lower than the average level for the

general population, and there have been similar findings in other studies (Rubins

et al. 1999, Tonkins and Hunt 2000). A major Swedish study to ascertain heart-

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disease risk factors found that the best predictor of heart disease was the

concentration of apo b proteins. Half of the patients who died during the course

of the study had normal levels of low density lipoproteins but high apo b numbers3

(Walldius 2001). The key point here is that low density lipoproteins and low density

lipoproteins cholesterol are not one and the same thing. The low density lipoproteins

carries the cholesterol, but the amount of cholesterol in each low density lipoproteins

particle will vary.

Goffman et al. (1996) has described the measurement of total cholesterol ‘false

and highly dangerous guide’. In fact the relationship between cholesterol and

cardiovascular disease is not clear raising important questions about its use as a risk

marker. While there may be an association, as Colpo (2006) argues, this does not

automatically equate to causation. However to truly unravel the relationship it is

necessary to examine three distinct population groups: those under and over the age

of 50, women and those with a previous cardiovascular disease episode.

One of the biggest studies into the relationship between cholesterol and deaths

from CHD is the Framlingham study involving 1959 men and 2415 women aged

between 31 and 65 years of age (Kannel et al. 1979). The researchers claimed that the

results showed conclusively that cardiovascular disease was linked to high

cholesterol. However, a follow up study (Anderson et al. 1987) found that

reductions in cholesterol levels before the age of 45 were associated with increases

in mortality in older age groups (11% increase in total mortality and a 14% increase

in CHD mortality per 1 mg/dl per year drop in cholesterol levels). When ‘translated’

into the units used in the UK, this becomes a 1 mmol/1 fall in cholesterol levels is

equal to a (39x11%) increase in the risk of total mortality which is 429%. To put this

into context, if your cholesterol were to fall from 5 to 4 mmol.1, your risk of dying

would increase by more than 400%. Not only that, but your risk of dying from

cardiovascular disease would increase by 39x14% ¼ 546% (Kendrick 2007a). What

this means, in short, is that before the age of 50, total cholesterol levels in both men

and women showed no relationship with cardiovascular disease or total mortality.

Many studies have replicated this finding and, more importantly, have shown that

over the age of 50 high cholesterol levels are not associated with cardiovascular

disease, stroke or higher overall mortality (Forette et al. 1982, Siegel 1987, Nissinen

et al. 1989, Simons et al. 2001, Abbott et al. 2002, Brescianini 2003) and,

significantly, shown that higher levels of cholesterol are predictive of increased

survival and increased longevity in older age groups. These findings were much more

marked among women at all ages. Research suggests that contrary to the logic of

cholesterol reduction it is low cholesterol which may in fact be a problem (Ulmer

et al. 2004). They also found that women with higher cholesterol had improved

health outcomes corroborating earlier studies that showed that women with high

cholesterol concentrations (4295 mg/dl) had lower rates of myocardial infarction

than men with lower concentrations (<204 mg/dl) and that increases of 10 mg/dl in

HDL (high density lipoproteins) were associated with a reduction of coronary risk in

women (Bush 1988, p. 60).

What this brief examination of the evidence has shown studies have largely failed

to show a consistent link between cholesterol levels and cardiovascular disease and it

is difficult to ‘prove’ that a high cholesterol level is either a cause or a risk marker for

cardiovascular disease. What can be clearly shown is that it is NOT a risk factor for

women (at any age) and it is not a consistent risk factor for men, especially those

over 70. More importantly, lowering cholesterol levels is associated with increased

Health, Risk & Society 39

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total mortality and, therefore, challenges the central assumption upon which

screening is based that high cholesterol levels are the problem.

Clearly the relationship between cholesterol levels and cardiovascular disease is

not as clear as the guidelines suggest. Measurement of total cholesterol is widely used

as a marker but ignores relationships between low density lipoproteins, and high

density lipoproteins and very low density lipoproteins is generally never considered.

However even the exact relationship between the low density lipoproteins and high

density lipoproteins levels and cardiovascular disease is not clear. The evidence

suggests that we should be cautious about identifying these as markers of risk. The

situation is also complex as the effects of cholesterol are different for different age

groups and for men and women. Finally a further problem is that measuring low

density lipoproteins and high density lipoproteins is not the same as measuring

actual cholesterol levels. Despite this, substantial effort is placed on reducing

cholesterol levels as a method for preventing cardiovascular disease. Two

approaches are available to practitioners: reductions through dietary changes and

prescribing statins. However, as the evidence on the link between cholesterol and

cardiovascular disease shows, there are important questions about why this is done

and what the implications are for mortality and morbidity.

Reducing cholesterol: Reducing dietary fat and the role of statins

The orthodox approach to reducing cholesterol through diet is to recommend a

reduction in fat intake and that people should, in particular, reduce their

consumption of saturated fats and increase the carbohydrate intake. For example

The Dietary Guide for Americans published by the US Government (2000)

recommends that people should keep the consumption of saturated fat low and

avoid foods high in cholesterol while in the UK the message focuses on lowering

saturated fat consumption (http://www.eatwell.gov.uk/healthydiet/fss/fats/satfat/).

In broad terms the orthodoxy is that saturated fats in the diet are ‘bad’ while

unsaturated fats are ‘good’, and that the consumption of saturated fats will increase

the levels of ‘bad’ cholesterol. But, a clear correlation between saturated fat

consumption and serum cholesterol levels is difficult to find (Colpo 2006). Early

studies on the links between dietary fat intake and heart disease were able to show

that it was the very low density lipoproteins and low density lipoproteins levels that

seemed to be predictors of heart disease (not the cholesterol levels).

However, it has been shown that individuals with similar saturated fat intakes

can posses markedly different serum cholesterol concentrations, and serum

cholesterol levels are influenced by a whole host of factors aside from fat intake

including stress, physical activity, obesity, illness, smoking, genetics, alcohol,

medicine use and even body position (Ravnskov 2000). In addition, studies suggest

that ‘dietary cholesterol . . . has an insignificant effect on blood cholesterol. It might

elevate cholesterol levels in a small percentage of highly sensitive individuals, but for

most of us, its clinically meaningless’ (Taube 2009, p. 19). Also, those societies that

consume more saturated fat appear to have lower than expected cholesterol levels

and lower rates of heart disease. This has been borne out by studies of the Masai

(Sharper 1962, Mann et al. 1964, Biss 171, Colpo 2006, Kendrick 2007a) and in

European studies (Kendrick 2007a, Allender 2008b).

In a review of 18 of the largest trials that took place between 1955 and 2006 to

test the connection between diet and heart disease, Colpo (2006) only found two that

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produced a statistically significant reduction in deaths from coronary heart disease:

the St Thomas Athersclerotic Regression Study (STARS) and the Diet and

Reinfarction Trial (DART). However, in both cases the result was attributed not

to the lower intake of saturated fat, but to an increased intake of fish oils, and in the

case of the DART trial the fish oil group not only had a much lower rate of heart

disease but a higher cholesterol level than the control group. Other studies have

found similar findings (Little et al. 1965, Papp et al. 1965, Bassett et al. 1969, Moore

1990, Yli-Jama et al. 2002, Lemaitre et al. 2003, Kendrick 2007a). Finally, a

Cochrane Review in 2001 on ‘reduced or modified dietary fat for preventing

cardiovascular disease’ concluded that the diets, whether low fat or cholesterol

lowering, had no effect on longevity and no significant effects on cardiovascular

events (Hooper et al. 2001). A similar review in 2006 concluded that ‘multiple risk

factor intervention has no effect on mortality’ (Ebrahim et al. 2006).

The research evidence is relatively clear about the relationships between

cholesterol, dietary fat intake and heart disease. Eating cholesterol does not raise

blood cholesterol levels, but very low density lipoproteins levels are raised by eating

carbohydrates and, in fact, a high fat diet lowers very low density lipoproteins.

Finally, low density lipoproteins levels (measured as bad cholesterol) are unaffected

by what you eat. Thus there is a misconception that high dietary fat leads to high

cholesterol levels (especially ‘bad’ cholesterol) and thus heart disease. Because of the

difficulties of using diet to control cholesterol levels, as other aspects of diet affect

cholesterol levels (e.g. carbohydrates), we have seen the increasing use of

pharmaceutical responses to reducing cholesterol levels through the use of statins.

Statins are widely prescribed for reducing serum cholesterol levels and are the

main weapon in the clinical armoury.4 Current prescribing guidelines issued by

NICE (2008) and UK Professional bodies (British Cardiac Society et al. 2000)

suggest that patients be prescribed statins for adults who have a 20% or greater

10-year risk of developing cardiovascular disease.

Initial studies of statins, such as the Clofibrate Trial, did not demonstrate very

good results (Moore 1990), but more recent trials have shown that statins can, and

do, reduce cholesterol levels to a far greater degree than diet alone. However, as

demonstrated above, blood lipid levels are hardly a consistent or reliable predictor of

cardiovascular disease, and any association between serum cholesterol and

cardiovascular disease is, at best, secondary. In addition, as we discuss below, any

affect on cardiovascular disease has to be considered alongside the affects of statins

on overall morbidity and mortality. In a randomised control trial of pravastatin

therapy on risk of stroke, White et al. (2000) reported a 19% relative reduction in

risk, although the absolute risk reduction was 0.8%, a reduction of less than 1 stroke

per 1000 population treated. In contrast, the PROSPER trial (involving high risk

elderly patients) found that the highest survival rates in both the treatment and the

control groups were among those with the highest (emphasis in original) low density

lipoproteins cholesterol levels (Shepherd et al. 2002). Similarly the Japanese Lipid

Intervention Trial (J-LIT, a 6-year study of over 47,000 patients treated with

simvastatin) found that those with a total cholesterol level of 200–219 mg/dl had a

lower rate of coronary heart events than those whose levels were above or below this

range. The lowest overall mortality rate was seen in patients whose total and low

density lipoproteins cholesterol levels were between 200–259 mg/dl. The highest

mortality was observed among those whose cholesterol levels were below 160 mg/dl

(Kawashir et al. 2006). Trials have shown, however, that statin therapy is beneficial

Health, Risk & Society 41

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for males who have already had a coronary event and who are over 50 years of age.

It is suggested that this effect seems to be independent of the cholesterol lowering

effects of these drugs (Colpo 2006).

One major problem with statin trials is that some of the largest (and most

influential) studies which have been hailed as showing beneficial outcomes from

statin use are, according to Ellison (2006), playing ‘statistical games’. He points out

that ‘[b]efore you can consider the safety and effectiveness of a drug, you must first

understand the statistical terminology, in particular it is important to understand the

distinction between ‘‘total mortality’’, absolute risk reduction and relative risk

reduction’ (Ellison 2006, p. 113). The easiest one to understand is total mortality as,

quite simply, it demonstrates whether or not the drug increases the overall life

expectancy. This is important because, as already hinted at above, while a drug

might prevent a particular disease, it may also kill you from some other condition,

such as cancer. When reporting total mortality, this can be expressed in either

relative or absolute terms. Absolute risk reduction (ARR) refers to the actual

difference in risk reduction between the treated and the non-treated group. However,

studies often use the relative risk reduction which exaggerates benefits. Many of the

trials that have claimed the success of statins use the relative risk reduction. For

example, the PROSPER study mentioned above claimed a 15% relative risk

reduction although in fact the trial showed that Pravachol provided no reduction in

heart attack or stroke among those who had no previous signs of cardiovascular

disease (primary prevention) and an absolute risk reduction of 4.3% among those

who did (secondary prevention).

Interestingly, statins can confer a wide variety of favourable cardiovascular

effects, to certain groups, but what also seems clear is that these effects are

independent of cholesterol reduction (Colpo 2006). Despite this, the medical

orthodoxy is still that it is the cholesterol lowering effect that gets the results. This is

despite evidence to suggest that independently of any affect on cardiovascular

disease, statins have been shown to have clear associations with wider morbidity and

mortality (Rizvi et al. 2002, De Graff et al. 2004, LaRosa et al. 2005, Bamji 2008,

Campbell 2008, Sathasivam 2008). The TNT study which was launched in March

2005 randomly assigned 10,001 cardiovascular disease patients with cholesterol

levels of less than 130 mg/dl to varying doses of atorvastatin (LaRosa et al. 2005).

They found was that there was a 20% relevant risk reduction for the high dose group

but there was no difference between the study group and the control group in overall

mortality. Specifically, cancer deaths were 13% higher in high dose group, while

non-traumatic deaths from causes other than cancer were increased by over a third.

Similarly, other studies have shown that the use of statins has produced a

reduction in risk from cardiovascular disease in those (men) who have already had a

coronary event but not necessarily in overall morbidity/mortality, and that these

advantages seem to occur even though the cholesterol levels between the groups

remain similar (Ridker et al. 1998). In order to examine the clinical evidence for the

national recommendations on cholesterol monitoring, Hayward et al. (2006)

reviewed all the controlled trials, cohort studies and case controlled studies that

examined the independent relationship between low density lipoproteins cholesterol

and major cardiovascular outcomes in patients with low density lipoproteins

cholesterol less than 3.36 mmol/l (<130 mg/dl) (p. 520). They concluded that there

was no evidence that ‘. . . the degree to which low density lipoproteins cholesterol

responds to a statin independently predicts the degree of cardiovascular risk

42 A. Hann and S. Peckham

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reduction’ (Hayward et al. 2006, p. 520). The limitation of statin therapy is

particularly important for women as studies have consistently demonstrated that

there is no significant reduction in mortality for them (Miettinen et al. 1997, Jenkins

2003, Sliva et al. 2006, Kendrick 2007b, Capewell 2008). Eisenberg and Wells (2008)

has claimed that the makers of atorvastatin (Lipitor) ‘failed to disclose the absence

of benefits for women, who should be entitled to compensation to recoup the costs of

treatment’ (p. 9).

There are further complications as there is considerable evidence that, for some

groups of people, statin use is counterproductive due to adverse drug effects. Trials

which consider only mortality would miss changes in morbidity. This also raises the

question of how qualitatively distinctive risks are to be combined? (Heyman

Forthcoming). In 2001, Bayer were forced to remove cerivastatin (Baycol) from the

market as Baycol users began to complain of adverse effects, including serious

conditions like rhabdomyolysis5 that could lead to death, paralysis and kidney

failure. Bayer claimed that the adverse effects were due to ‘misuse’ of the drug, and

relabelled their product. But despite this, by August 2001, the FDA had received so

many reports of rhabdomyolysis occurring among Baycol patients using the drug

(without any other drug combination) to warrant a Baycol recall. More than 12,000

Baycol lawsuits were filed and, so far, Bayer has settled 2312 Baycol cases for an

estimated US$872 million, with a further 9278 Baycol cases pending. Baycol is not

the only statin that causes muscle weakness and damage (Hammer 2003, Draeger

et al. 2006, Seehusen et al. 2006). It is increasingly recognised that many people on

statins will suffer a wide variety of adverse effects. It is estimated that, in the USA,

some 1.5 million people per year will experience a muscle related adverse event6

(Sathasivam 2008). Other problems associated with statin use include statin-

associated neuropathy7, extreme muscle pain and weakness, cognitive dysfunction,

(especially with a drug called Lipitor) erectile dysfunction and loss of libido (Roth

1992, Muldoon et al. 2000, Rizvi et al. 2002, Wagstaff 2003, De Graff et al. 2004,

Bamji 2008, Campbell 2008). Graveline (2004) comments that, when he was a

medical student, transient global amnesia (TGA) was very rare but, in recent years, it

has become increasingly common. Both TGA and more limited memory loss have

been linked to atorvastatin, simvastatin, pravastatin and fluvastatin, and both the

muscle weakness and the cognitive dysfunction have both been linked to the

depletion of Coenzyme Q10. The ‘CoQ10 robbing effects’ (Colpo 2006) of statins has

(ironically) been linked to an increased risk of congestive heart failure. Although the

link between congestive heart failure and statins is not proven, the correlation has

been remarked upon by others (Langsjoen and Langsjoen 2005, Gregor 2006).

Statins have also been linked to various kinds of cancer. Newman and Hulley (1996)

noted the link between cancer incidence and the use of statins in rodents, but

subsequent studies have also suggested links (Sacks et al. 1998, Shepherd et al. 2002,

Iwata et al. 2006).

Discussion

The evidence we present here demonstrates that the assumed link between

cholesterol levels, dietary fat and cardiovascular disease morbidity and mortality

is certainly not linear or even well established. This raises the question of why the

conventional view that they are linked was adopted and is so widely accepted. Taube

(2009) suggests that one of the crucial factors in the rise of the dietary fat equals

Health, Risk & Society 43

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heart disease thesis was the existence of a ‘critical mass’ of clinicians who were able

to dominate the thinking of the time, highlighting the role of the Gold Effect. There

is strong and consistent evidence that demonstrates that the measurement of, and

taking steps to reduce, cholesterol levels are not effective methods for predicting or

preventing cardiovascular disease. In particular, measuring total cholesterol reveals

nothing about the relative levels of very low density lipoproteins and low density

lipoproteins.

The strength of the orthodoxy is clearly observable in research studies where

outcomes that do not concur with the orthodoxy are considered odd. The Honolulu

Heart Program (a 20-year longitudinal study of changes in lipid and serum cholesterol

levels) was undertaken to investigate discrepancies arising from studies examining the

relationship between serum cholesterol and all cause mortality in elderly people which

had shown contrasting results. However they found that: ‘Only the group with low

cholesterol [our emphasis] concentration at both examinations had a significant

association with [higher] mortality’ (Schatz et al. 2001, p. 351). They were: ‘unable to

explain their results’ but concluded that their findings did ‘cast doubt on the scientific

justification for lowering cholesterol’ (Schatz et al. 2001, p. 351).

This orthodox view also pervades the broader arena of public health. Taube

(2009) argues that ‘mainstream nutritional science has demonised dietary fat, yet 50

years and hundreds of millions of dollars of research has failed to prove that eating a

low-fat diet will help you live longer’(p. 1)8. Taube also points out the influence of

the food industry in promoting the ‘healthy eating’ message which has become

synonymous with avoiding fat in the diet. He comments: ‘The low fat gospel spreads

farther by a kind of osmosis, continually reinforced by physicians, nutritionists,

journalists, health organisations and consumer advocacy groups such as (in the

USA) the Center for Science in the Public Interest, which refers to fat as the ‘‘greasy

killer’’. In America, we no longer fear God or the Communists, but we fear

fat’(Taube 2001, p. 30). Cholesterol screening is an imprecise science and given that

measurement of cholesterol is also by proxy (i.e. the measurement of low density

lipoproteins and high density lipoproteins) the question of why it has been chosen as

an indicator is one that requires answering.

As might be predicted by the Gold Effect there appears to be a critical mass of

opinion and opinion leaders who have concurred with the orthodox view and this

then serves to influence policy decisions. Fundamentally, the development of policy

is based upon values and the use of evidence is influenced by both ideological

positions and what Sabatier has described as core beliefs and thus selective use of

evidence is likely (Sabatier and Jenkins Smith 1993). Dobrow et al. (2004) have

argued that it is important to consider how evidence is interpreted (recognition of the

relevance, appropriateness and utility of the research) and how it is used to support

or justify a decision. Importantly, contextual factors have a major influence, for

example whether the evidence is in tune with prevailing ideology and the political

acceptability of different decisions. The wide acceptance in medical, public health,

commercial and lay communities of the link between fat, cholesterol and heart

disease may explain why cholesterol screening and reduction are such key elements

of preventive health strategies. The Gold Effect demonstrates how the process by

which an idea becomes the received wisdom, and becomes embedded into ‘what

everyone knows’. The lower the better message for cholesterol levels (and saturated

fat consumption) is being constantly reinforced by medical orthodoxy, health

promotion leaflets and the ‘health media’, not to mention the low fat ‘healthy’ food

44 A. Hann and S. Peckham

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industry. Certainly it is difficult to escape the message that cholesterol (and fat) is

bad for you, and many foods are now marketed on the basis that they are ‘good for

your heart’ or that they lower cholesterol levels. In addition, pharmaceutical

companies have invested heavily in cholesterol lowering drugs, and have been very

active in marketing these products to GPs. Direct marketing to consumers in the

USA focuses substantially on the bad effects of high cholesterol and the need for

statins (Abramson 2004).

Once a risk factor has been ‘legitimised’ (such as in the UK where national

guidance and financial incentive schemes have been put in place), practitioners are

encouraged to identify those potentially at risk and take measures to bring their

levels of cholesterol within national guidelines. National guidelines are developed to

ensure standardisation of practice. They then become enshrined in the mechanisms

of health systems and health surveillance. Because guidelines are established by

bodies such as NICE, professional organisations such as the British Cardiac Society

are core constituents of the Quality and Outcomes Framework (itself a part of the

general practice contract) which further embeds this orthodoxy in practice. For most

GPs, the most obvious approach is to use statins as they have been shown to be the

most effective way of reducing cholesterol levels. While this may ‘fit’ the accepted

orthodoxy for the role of cholesterol and statins as we have shown, it is not

supported by the evidence on the link between cholesterol levels and morbidity and

mortality. It is true that statins might enhance life expectancy for certain groups,

particularly men with a previous cardiovascular disease episode, but this is likely to

be at the price of reduced quality of life. More importantly, this reduction in quality

of life also occurs for sub-groups of the population for whom benefits have not even

been demonstrated. For males, the total mortality data shows that for men with

already diagnosed heart disease, such as a previous infarction or angina, they do

have protection against further cardiovascular disease, though this may be offset by

an increase in all cause mortality. For women, lowering of cholesterol and the use of

statins confers no health benefit at all, but if GPs are incentivised to undertake

opportunistic cholesterol monitoring they are more likely to screen women as they

make up a larger proportion of GP consultations.

The proposed extension of screening in health checks for people aged 40–74 is

currently being rolled out across the UK and will form part of the core general

practice contract. Cholesterol screening will be one of a number of checks to identify

patients at risk from vascular disease. Health checks will be undertaken every 4 years

and are likely to lead to a substantial increase in statin use even though it is widely

accepted that most people will not benefit and may in fact suffer worse morbidity

and mortality, a fact even accepted by the national clinical director for

cardiovascular disease in England (Smith 2009). In addition, concerns about the

lowering of the risk thresholds for statin treatment will result in large numbers of

patients becoming eligible for treatment, the NHS strategy will mean that over 80%

of English men aged 65–74 will be categorised as high risk, and therefore a fair

proportion of middle-aged adults will be on lifelong treatment, despite evidence to

suggest that this could lead to higher morbidity and mortality.

Conclusions

In this paper we have sought to demonstrate the weakness of cholesterol as a

screening test for cardiovascular disease. The weak link between cholesterol levels

Health, Risk & Society 45

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and cardiovascular disease has been acknowledged for many years, yet cholesterol

measurement remains a key screening test for risk of cardiovascular disease.

However, the situation is further complicated by the approach adopted in general

practice that has seen the use of statins as first line drugs prescribed to lower

cholesterol despite evidence that they should be used more selectively. That the

inclusion of serum cholesterol measurement is justified on evidence-based grounds is

clearly open to challenge given its poor performance. Debates about the importance

of serum cholesterol levels and the use of statins continue to feature in the medical

press, but in the meantime the Quality and Outcomes Framework incentive remains

in place, potential screening of adults is increasing through the health check policy

and new patients are being screened for cholesterol levels and prescribed statins.

Tackling cardiovascular disease is a complex issue and the focus on cholesterol as

a risk marker will not provide the answer to reducing cardiovascular disease

morbidity and mortality. The first step to a sensible policy would be to remove

cholesterol testing as a primary approach to screening for risk. More education is

needed for health professionals about the nature of dietary fat and its relationship to

cholesterol and cardiovascular disease so that they at least are in a better position to

inform their patients. The incorporation of cholesterol levels within Quality and

Outcomes Framework and the new health checks should be reviewed and clearer

guidelines about risk and benefit developed to identify more appropriate and

effective risk assessment. It would also help if journals had clearer guidelines on

publishing results to ensure that both absolute and relative risks are identified in

papers reporting on trials. Finally, we need to remove the pressures from the

‘cholesterol industry’ on practitioners but most important we should not

contemplate direct marketing of statins to the consumer in the UK.

Notes

1. Unless stated otherwise future references to cholesterol or serum cholesterol in this paperrefer to total cholesterol.

2. Atherosclerotic plaques develop not on the surface of the artery, but between the innerand outer walls. They are comprised of fat and cholesterol, but also arterial muscle tissue,white blood cells, collagen, calcium and blood platelets.

3. DL comes in at least seven distinct subtypes, characterised by size and density. Thelipoprotein has a single protein – apo B – which serves as the structural foundation. It isnot viable to screen for apo B levels on a routine basis.

4. There are seven forms of statin drugs with a range of effectiveness and which are availablein various doses (usually between 5 and 40 mg per tablet) and prescribed at up to 80 mgper day. Statin drugs fall into two groups: fermentation-derived or synthetic. Thefermentation-derived statins include lovastatin (Mevacor, Advicor, or Altoprev),simvastatin (Zocor), and pravastatin (Pravachol or Pravigard), while the synthetic groupis composed of fluvastatin (Lescol), atorvastatin (Lipitor), Pitavastatin (Livalo), androsuvastatin (Crestor).

5. This rare disorder occurs when a large number of skeletal muscle cells die, subsequentlyreleasing massive amounts of muscle protein into the bloodstream. The muscle proteinsaturates the kidneys, effectively overwhelming their filtration capacities.

6. For a detailed discussion of the problems surrounding the complex calculationssurrounding risks and benefits of medical interventions see Hayman, B. et al., 2010.Risk, safety and clinical practice: healthcare through the lens of risk. Oxford: OxfordUniversity Press.

7. Malfunction or disease pathology of nerves. Peripheral neuropathy refers to a disease ordegenerative state of peripheral nerves resulting in pain, numbness, and muscle weakness.

8. The implication being that you are less likely to suffer a cardiac event.

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